yycg histidine kinase: Topics by WorldWideScience.org

Generation of a proton motive force by histidine decarboxylation and electrogenic histidine/histamine antiport in Lactobacillus buchneri.

A histidine kinase protein (Cph1) with sequence homology and spectral characteristics very similar to those of the plant phytochrome has been recently identified in the cyanobacterium Synechocystis...Full Text Available

2000-01-01

Gene discovery in the Acanthamoeba castellanii genome

Lactobacillus buchneri ST2A vigorously decarboxylates histidine to the biogenic amine histamine, which is excreted into the medium. Cells grown in the presence of histidine generate both a transmembrane...Full Text Available

1993-05-01

Synthesis of histidine-stabilized cadmium sulfide quantum dots: Study of their fluorescence behaviour in the presence of adenine and guanine

Acanthamoeba castellanii is a free-living amoeba found in soil, freshwater, and marine environments and an important predator of bacteria. Acanthamoeba castellanii is also an opportunistic pathogen of clinical interest, responsible for several distinct diseases in humans. In order to provide a genomic platform for the study of this ubiquitous and important protist, we generated a sequence survey of approximately 0.5 x coverage of the genome. The data predict that A. castellanii exhibits a greater biosynthetic capacity than the free-living Dictyostelium discoideum and the parasite Entamoeba histolytica, providing an explanation for the ability of A. castellanii to inhabit adversity of environments. Alginate lyase may provide access to bacteria within biofilms by breaking down the biofilm matrix, and polyhydroxybutyrate depolymerase may facilitate utilization of the bacterial storage compound polyhydroxybutyrate as a food source. Enzymes for the synthesis and breakdown of cellulose were ...

2005-08-01

British Library Electronic Table of Contents (United Kingdom)

Cadmium sulfide particles have been synthesized in the aqueous medium using the amino acid histidine as a stabilizing agent. These particles demonstrate the phenomenon of size quantization effect. The fluorescence of histidine-stabilized CdS was found to be enhanced and quenched by the addition of DNA bases adenine and guanine, respectively. The fluorescence enhancement of CdS in the presence of adenine has been explained on the basis of interaction between the quantum dot stabilizer and the amino group of adenine. Quenching of CdS fluorescence by guanine occurs due to interaction of the substrate with the quantum dot surface.

2010-01-01

A modified immunoblot method to identify substrates of protein kinases

KoreaScience (Korea)

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Src Kinase Inhibition Decreases Thrombin Induced Injury and Cell Cycle Re-Entry in Striatal Neurons

Rapid detection of epidermal growth factor receptor mutations with multiplex PCR and primer extension in lung cancer

Since Src kinase inhibitors decrease brain injury produced by intracerebral hemorrhage (ICH) and thrombin is activated following ICH, this study determined whether Src kinase inhibitors decrease...Full Text Available

2008-05-01

Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available

EhMAPK, the Mitogen-Activated Protein Kinase from Entamoeba histolytica Is Associated with Cell Survival

The activity of Src-related protein-tyrosine kinases is repressed by the phosphorylation of a conserved carboxyl-terminal tyrosine by another cytoplasmic protein-tyrosine kinase termed p50csk. In this...Full Text Available

1994-05-24

Cardiac Myosin Is a Substrate for Zipper-interacting Protein Kinase (ZIPK)*

Mitogen Activated Protein Kinases (MAPKs) are a class of serine/threonine kinases that regulate a number of different cellular activities including cell proliferation, differentiation, survival and...Full Text Available

Activation of fat cell adenylate cyclase by protein kinase C

Zipper-interacting protein kinase (ZIPK) is a member of the death-associated protein kinase family associated with apoptosis in nonmuscle cells where it phosphorylates myosin regulatory light chain...Full Text Available

2010-02-19

AMP-Activated Protein Kinase: A Stress-Responsive Kinase with Implications for Cardiovascular Disease

Purified protein kinase C (C-kinase) from guinea pig pancreas and rat brain stimulated adenylate cyclase activity in purified rat adipocyte membranes. Cyclase stimulation occurred over 100 to 1000 mU/ml of C-kinase activity, required greater than 10 ..mu..M calcium, proceeded without a lag, was not readily reversible, and required no exogenous phospholipid. Moreover, C-kinase inhibitors, such as chlorpromazine and palmitoyl carnitine, inhibited selectively adenylate cyclase which was activated by C-kinase and calcium. Depending on assay conditions, 10 nM 12-0-tetradecanoylphorbol-13-acetate (TPA) either enhanced or was required for kinase action on cyclase. Also, TPA plus calcium promoted the quantitative association of C-kinase with membranes. Adenylate cyclase activation by C-kinase was seen both in the presence and ...

1986-05-01

Phosphorylation of Annexin A1 by TRPM7 Kinase: A Switch Regulating the Induction of an ?-Helix

AMP-activated protein kinase (AMPK) was initially viewed as energy sensor and activated by increased intracellular concentrations of AMP following nutrient deprivation. Physiological or pathological...Full Text Available

2010-04-01

Structure and Function of NtCDPK1, a Calcium-dependent Protein Kinase in Tobccco

TRPM7 is an unusual bifunctional protein consisting of an α-kinase...Full Text Available

2011-03-29

KoreaScience (Korea)

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2000-05-01

Gamma interferon induces rapid and coordinate activation of mitogen-activated protein kinase (extracellular signal-regulated kinase) and calcium-independent protein kinase C in human monocytes.

Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors

Gamma interferon plays an important role in regulating the functional properties of mononuclear phagocytes. In the present study, the role of activated protein kinases in the mechanism of action of...Full Text Available

1994-07-01

Phosphorylation of sites 3 and 2 in rabbit skeletal muscle glycogen synthase by a multifunctional protein kinase (ATP-citrate lyase kinase)

The p90 ribosomal S6 kinases (RSKs) also known as MAPKAP-Ks are serine/threonine protein kinases that are activated by ERK or PDK1 and act as downstream effectors of mitogen-activated protein kinase...Full Text Available

2007-12-01

pH and iodide ion effect on corrosion inhibition of histidine self-assembled monolayer on copper

A multifunctional protein kinase, purified from rat liver as ATP-citrate lyase kinase, has been identified as a glycogen synthase kinase. This kinase catalyzed incorporation of up to 1.5 mol of and)2numberSPO4/mol of synthase subunit associated with a decrease in the glycogen synthase activity ratio from 0.85 to a value of 0.15. Approximately 65-70% of the TUPO4 was incorporated into site 3 and 30-35% into site 2 as determined by reverse phase high performance liquid chromatography. This multifunctional kinase was distinguished from glycogen synthase kinase-3 on the basis of nucleotide and protein substrate specificities. Since the phosphate contents in glycogen synthase of sites 3 and 2 are altered in diabetes and by insulin administration, the possible involvement of the multifunctional kinase was explored. Glycogen synthase purified from ...

1985-10-05

Insulin-induced decrease in protein phosphorylation in rat adipocytes not explained by decreased A-kinase activity

Self-assembled monolayer (SAM) of histidine (His) was prepared on copper surface at various pH values. The effect of KI additives on corrosion protection efficiency of His SAM was also studied. The protection abilities of these films against copper corrosion in 0.5 M HCl aqueous solution were investigated using electrochemical impedance spectroscopy and polarization techniques. The results show that the film formed on the electrode is more stable at pH = 10 than that at other pH values. When the iodide ions were added into the His self-assembly solution (pH = 10), protection efficiency was further improved. The inhibition mechanism has been discussed by quantum chemical calculations.

2010-03-01

Perlinhibin, a Cysteine-, Histidine-, and Arginine-Rich Miniprotein from Abalone (Haliotis laevigata) Nacre, Inhibits In Vitro Calcium Carbonate Crystallization

In isolated rat adipocytes, insulin inhibits lipolysis to a greater extent than would be predicted by the decrease in (-/+)cAMP activity ratio of cAMP-dependent protein kinase (A-kinase), from which it was speculated that insulin promotes the dephosphorylation of hormone-sensitive lipase. They have examined the phosphorylation state of cellular proteins under conditions of varying A-kinase activities in the presence and absence of insulin. Protein phosphorylation was determined by SDS-PAGE electrophoresis of extracts from /sup 32/P-loaded cells; glycerol and A-kinase activity ratios were measured in the cytosolic extracts from control, non-radioactive cells. Increased protein phosphorylation in general occurred over the same range of A-kinase activity ratios, 0.1-0.3, associated with increased glycerol release. The insulin-induced decrease in lipolysis was associated with a decrease ...

1987-05-01

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The impact of a repeated bout of eccentric exercise on muscular strength, muscle soreness and creatine kinase.

We have isolated a 4.785 Da protein from the nacreous layer of the sea snail Haliotis laevigata (greenlip abalone) shell after demineralization with acetic acid. The sequence of 41...Full Text Available

2007-08-15

Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

The purpose of this study was to determine if there were any beneficial or detrimental effects regarding delayed onset muscle soreness (DOMS), serum creatine kinase (CK), and maximum concentric strength...Full Text Available

1994-12-01

Separation, Purification, and Comparative Properties of Chloroplast and Cytoplasmic Phosphoglycerate Kinase from Barley Leaves ¹

We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC...Full Text Available

2009-12-01

Phosphoglycerate kinase and triosephosphate isomerase from the hyperthermophilic bacterium Thermotoga maritima form a covalent bifunctional enzyme complex.

The chloroplast and cytoplasmic isoenzymes of phosphoglycerate kinase (PGK) (EC. 2.7.2.3) from Hordeum vulgare leaves have been separated and purified for the first time to apparent...Full Text Available

1990-06-01

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA

Phosphoglycerate kinase (PGK) from the hyperthermophilic bacterium Thermotoga maritima has been purified to homogeneity. A second larger enzyme with PGK activity and identical N-terminal sequence was...Full Text Available

1995-02-01

Involvement of AMP-activated-protein-kinase (AMPK) in neuronal amyloidogenesis

BackgroundAurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently...Full Text Available

Immunolocalization of phospho-S6 kinases: a new way to detect mitosis in tissue sections and in cell culture

AMP-activated-protein-kinase (AMPK) is a key sensor and regulator of cellular and whole-body energy metabolism and plays a key role in regulation of lipid metabolism. Since lipid metabolism...Full Text Available

2010-09-03

Expression and Characterization of the Mycobacterium tuberculosis Serine/Threonine Protein Kinase PknB

During a study on the mTor pathway in the rat kidney we observed a striking increase of the phosphorylation of the S6 kinase in mitosis. In cryostat sections of perfusion-fixed tissue mitotic cells...Full Text Available

2007-02-01

EFFECT OF AGE ON THE ROLE OF RHO-KINASE IN SHORT TERM PARTIAL BLADDER OUTLET OBSTRUCTION

PknB is a member of the newly discovered eukaryotic-like protein serine/threonine kinase (PSTK) family of proteins. The pknB gene was cloned and expressed in Escherichia coli....Full Text Available

1999-11-01

Development of small-molecule inhibitors of the group I p21-activated kinases, emerging therapeutic targets in cancer

ObjectivesWe examined the expression of Rho Kinase (ROK) isoforms in young and old rabbit’s detrusor smooth muscles (SM) during the progression of short term...Full Text Available

2008-03-01

Deficiency of Phosphoinositide 3-Kinase Enhancer Protects Mice From Diet-Induced Obesity and Insulin Resistance

The p21-activated kinases (PAKs), immediate downstream effectors of the small G-proteins of the Rac/cdc42 family, are critical mediators of signaling pathways regulating cellular behaviors and...Full Text Available

2010-09-01

Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons

OBJECTIVEPhosphoinositide 3-kinase enhancer A (PIKE-A) is a proto-oncogene that promotes tumor growth and transformation by enhancing Akt activity. However, the physiological functions...Full Text Available

2010-04-01

CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway

The mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation....Full Text Available

2009-12-29

Autoantibodies to BRAF, a new family of autoantibodies associated with rheumatoid arthritis

Recently, CID755673 was reported to act as a highly selective inhibitor of protein kinase D (PKD). In the course of experiments using CID755673, we noticed that it exerted unexpected stimulatory...Full Text Available

2010-01-01

Antisense Expression of the CK2 ?-Subunit Gene in Arabidopsis. Effects on Light-Regulated Gene Expression and Plant Growth1

IntroductionBRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known...Full Text Available

2010-01-01

Allosteric regulation of glycerol kinase by enzyme IIIglc of the phosphotransferase system in Escherichia coli and Salmonella typhimurium.

The protein kinase CK2 (formerly casein kinase II) is thought to be involved in light-regulated gene expression in plants because...Full Text Available

1999-03-01

AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of ?-catenin at Ser 552

The mechanism by which enzyme IIIglc of the bacterial phosphotransferase system regulates the activity of crystalline glycerol kinase from Escherichia coli has been studied, and the inhibitory effects...Full Text Available

1985-05-01

c-Jun N-terminal Kinase 2 Regulates Multiple Receptor Tyrosine Kinase Pathways in Mouse Mammary Tumor Growth and Metastasis

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent...Full Text Available

2010-04-23

The Protein Kinase SnRK2.6 Mediates the Regulation of Sucrose Metabolism and Plant Growth in Arabidopsis^[W]^[OA]

c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available

2011-01-01

Canonical and Alternative Pathways in Cyclin-Dependent Kinase 1/Cyclin B Inactivation upon M-Phase Exit in Xenopus laevis Cell-Free Extracts

In higher plants, three subfamilies of sucrose nonfermenting-1 (Snf1)-related protein kinases have evolved. While the Snf1-related protein kinase 1 (SnRK1) subfamily has been shown to share pivotal...Full Text Available

2010-05-01

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Crystal growth, structural and optical characterization of a semi-organic single crystal for frequency conversion applications

Cyclin-Dependent Kinase 1 (CDK1) is the major M-phase kinase known also as the M-phase Promoting Factor or MPF. Studies performed during the last decade have shown many details of how CDK1 is regulated...Full Text Available

Kinetic, spectroscopic and chemical modification study of iron release from transferrin; iron(III) complexation to adenosine triphosphate

Single crystals of semi-organic L-histidine hydrobromide have been grown by slow evaporation technique from a mixture of L-histidine and hydrobromic acid in aqueous solution at ambient temperature. From high-resolution X-ray diffraction analysis, the crystalline perfection of the grown crystal has been studied. Single crystal X-ray diffraction analyses, Nuclear Magnetic Resonance spectral analysis, Thermo-Gravimetry (TG), Differential Thermal Analysis (DTA) and hardness test have been employed to characterize the as-grown crystals. The UV cutoff wavelength of the grown crystal is below 300 nm and has a wide transparency window, which is suitable for second harmonic generation of laser in the blue region. Nonlinear optical characteristics have been studied using Q switched Nd:YAG laser (#lambda#=1064 nm). The second harmonic generation conversion efficiency of the grown crystals confirms their suitability for frequency conversion applications.

2010-12-15

Phospholemman: A Novel Cardiac Stress Protein

Amino acids other than those that serve as ligands have been found to influence the chemical properties of transferrin iron. The catalytic ability of pyrophosphate to mediate transferrin iron release to a terminal acceptor is largely quenched by modification non-liganded histine groups on the protein. The first order rate constants of iron release for several partially histidine modified protein samples were measured. A statistical method was employed to establish that one non-liganded histidine per metal binding domain was responsible for the reduction in rate constant. These results imply that the iron mediated chelator, pyrophosphate, binds directly to a histidine residue on the protein during the iron release process. EPR spectroscopic results are consistent with this interpretation. Kinetic and amino acid sequence studies of ovotransferrin and lactoferrin, in addition to human serum transferrin, have allowed the ...

1985-01-01

Cardiac Enzymes, Renal Failure and Renal Transplantation

Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM...Full Text Available

2010-08-01

c-JUN N-TERMINAL KINASE MODULATES OXIDANT STRESS AND PEROXYNITRITE FORMATION INDEPENDENT OF INDUCIBLE NITRIC OXIDE SYNTHASE IN ACETAMINOPHEN HEPATOTOXICITY

Diagnostic accuracy of the currently available serum markers of cardiac injury, such as myoglobin, creatine kinase and its myocardial isoform, are altered in patients with renal failure. It is shown...Full Text Available

2006-03-01

Up-Regulation of the RhoA/Rho-Kinase Signaling Pathway in Corpus Cavernosum from Endothelial Nitric-Oxide Synthase (NOS), but Not Neuronal NOS, Null Mice

Acetaminophen (APAP) overdose, which causes liver injury in animals and humans, activates c-jun N-terminal kinase (JNK). Although it was shown that the JNK inhibitor SP600125 effectively reduced...Full Text Available

2010-07-01

Structural features underlying selective inhibition of protein kinase CK2 by ATP site-directed tetrabromo-2-benzotriazole

We tested the hypothesis that the basal release of nitric oxide (NO) from endothelial cells modulates contractile activity in the corpus cavernosum (CC) via inhibition of the RhoA/Rho-kinase signaling...Full Text Available

2010-04-01

Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiae

Two novel crystal structures of Zea mays protein kinase CK2α catalytic subunit, one in complex with the specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) and another...Full Text Available

2001-11-01

Phosphorylation of ?6-Tubulin by Protein Kinase C? Activates Motility of Human Breast Cells*

BackgroundWhen eukaryotic cells are deprived of amino acids, uncharged tRNAs accumulate and activate the conserved GCN2 protein kinase. Activated Gcn2p up-regulates the general amino...Full Text Available

Kappa-opioid receptor activation during reperfusion limits myocardial infarction via ERK1/2 activation in isolated rat hearts

Engineered overexpression of protein kinase Cα (PKCα) was previously shown to endow nonmotile MCF-10A human breast cells with aggressive motility. A traceable mutant of PKCα...Full Text Available

2009-06-26

Involvement of stress-activated protein kinase and p38 mitogen-activated protein kinase in mIgM-induced apoptosis of human B lymphocytes

BackgroundWe investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection...Full Text Available

2011-05-01

Evolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Despite intensive efforts, the intracellular signaling pathways that mediate apoptosis remain unclear. The human B lymphoma cell line, B104, possesses characteristics that make it an attractive model...Full Text Available

1996-11-26

A New Metal-Binding Site for Yeast Phosphoglycerate Kinase as Determined by the Use of a Metal-ATP Analog

The bifunctional rat liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (ATP:D-fructose-6-phosphate 2-phosphotransferase/D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 2.7.1.105/EC...Full Text Available

1989-12-01

(-)-Epigallocatechin Gallate Regulates CD3-mediated T Cell Receptor Signaling in Leukemia through the Inhibition of ZAP-70 Kinase*

Suicide substrate β, γ-bidentate Rh(III)ATP (RhATP) was used to map the metal ion-binding site in yeast phosphoglycerate kinase (PGK). Cleavage of the RhATP-inactivated enzyme with...Full Text Available

1997-02-01

Oxidation of aromatic alcohols on zeolite-encapsulated copper amino acid complexes

The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available

2008-10-17

Oriented immobilization of proteins on grafted porous polymers

Copper complexes of the amino acids histidine, arginine and lysine have been introduced into the supercages of zeolite Y and, for the first time, into the large intracrystalline cavities of zeolites EMT and MCM-22. The resulting host/guest compounds are characterized by X-ray powder diffraction, UV/VIS-spectroscopy in the diffuse reflectance mode and by catalytic tests in the liquid-phase oxidation of aromatic alcohols (viz. benzyl alcohol, 2- and 3-methylbenzyl alcohol and 2,5-dimethylbenzyl alcohol) with tertiary-butylhydroperoxide as oxidant. It was observed that intracrystalline copper-amino acid complexes possess remarkable catalytic activity, yielding the corresponding aromatic aldehydes and acids. (orig.)

1998-12-31

The hippo pathway in biological control and cancer development

The modification of polymers by radiation grafting has been utilized for several decades. The penetrability of gamma rays allows to modify the internal surfaces of porous materials retaining its mechanical properties. In recent years applications of these materials to obtain chromatographic supports and biocatalysts have been reported. In this work, we described the grafting of glycidyl methacrylate (GMA) onto a macroporous polysulfone polymer. Reproducible amount of grafting, from 10% to 60% was obtained by choosing favourable monomer concentration and gamma radiation doses from 6 kGy up. Afterwards, iminodiacetic acid (IDA) and amino phenyl arsine oxide (PAO) were covalently attached to the grafted polyGMA, in correspondence with the grafting degree. Later on, a recombinant histidin-patch thioredoxin protein (HP-rTrx) was immobilized onto this surface by two different ways, involving specific protein orientations. The first one involves an IDA-Ni{sup 2+} complex ...

2003-08-01

British Library Electronic Table of Contents (United Kingdom)

Abstract The Hippo pathway is an evolutionally conserved protein kinase cascade involved in regulating organ size in vivo and cell contact inhibition in vitro by governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is linked to cancer development. Its first core kinase Warts was identified in Drosophila more than 15 years ago, but it gained much attention when other core components of the pathway were identified 8 years later. Major discoveries of the pathway were made during past several years. The core kinase components Hippo, Salvador, Warts, and Mats in the fly and Mst1/2, WW45, Lats1/2, and Mob1 in mammals phosphorylate and inactivate downstream transcriptional co-activators Yorkie in the fly, Yes-associated protein (YAP) and transcriptional co-activator with ...

2011-01-01

Phorbol esters, protein kinase C, and thyroxine 5 prime -deiodinase in brown adipocytes

Inhibition of the heterotetrameric K++ channel KCNQ1/KCNE1 by the AMP-activated protein kinase

Protein kinase C activity has been identified in the rat brown adipocyte. About 60% of this activity is found in the cytosolic fraction under basal conditions, and 12-O-tetradecanoylphorbol 13-acetate (TPA) causes a rapid shift from the cytosol to the particulate fraction. Norepinephrine and phenylephrine causes a similar redistribution that can be blocked by prazosin but not by alprenolol. {alpha}{sub 1}-Adrenergic agonists cause three- to fivefold stimulation of type 2 iodothyronine 5{prime}-deiodinase activity in brown adipocytes. TPA has no effect on basal deiodinase activity and reduces the response of the enzyme to {alpha}{sub 1}-adrenergic agonists. These results suggest that the translocation of protein kinase C from cytosol to particulate fraction is not sufficient to increase deiodinase activity but can modulate the {alpha}{sub 1}-adrenergic agonist-mediated responses in these cells.

1988-03-01

British Library Electronic Table of Contents (United Kingdom)

Abstract The heterotetrameric K++-channel KCNQ1/KCNE1 is expressed in heart, skeletal muscle, liver and several epithelia including the renal proximal tubule. In the heart, it contributes to the repolarization of cardiomyocytes. The repolarization is impaired in ischemia. Ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK has previously been shown to downregulate the epithelial Na++ channel ENaC, an effect mediated by the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates KCNQ1/KCNE1. To this end, cRNA encoding KCNQ1/KCNE1 was injected into Xenopus oocytes with and without additional injection o...

2011-01-01

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Adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib

British Library Electronic Table of Contents (United Kingdom)

Abstract Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis o...

2011-01-01

skittles, a Drosophila phosphatidylinositol 4-phosphate 5-kinase, is required for cell viability, germline development and bristle morphology, but not for neurotransmitter release.

Use of clopidogrel in the reduction of myocardial damage during percutaneous coronary intervention

The phosphatidylinositol pathway is implicated in the regulation of numerous cellular functions and responses to extracellular signals. An important branching point in the pathway is the phosphorylation...Full Text Available

1998-12-01

The Receptor Tyrosine Kinase FGFR4 Negatively Regulates NF-kappaB Signaling

It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK)/creatinine kinase myocardial band (CK-MB) elevations and...Full Text Available

2009-01-01

The Dynamical Mechanism of Auto-Inhibition of AMP-Activated Protein Kinase

BackgroundNFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as...Full Text Available

Serotype- and strain- dependent contribution of the sensor kinase CovS of the CovRS two-component system to Streptococcus pyogenes pathogenesis

We use a novel normal mode analysis of an elastic network model drawn from configurations generated during microsecond all-atom molecular dynamics simulations to analyze the mechanism of auto-inhibition...Full Text Available

2011-07-01

Role of bile salt in regulating Mcl-1 phosphorylation and chemoresistance in hepatocellular carcinoma cells

BackgroundThe Streptococcus pyogenes (group A streptococci, GAS) two-component signal transduction system CovRS has been described to be important for pathogenesis...Full Text Available

Regulation of hyaluronan secretion into rabbit synovial joints in vivo by protein kinase C

BackgroundGlycochenodeoxycholate (GCDA) is one of the major human bile salts. Bile salts stimulate cell survival and proliferation through the mitogen-activated protein kinase, but...Full Text Available

Regulation of ROMK1 Channels by Protein-tyrosine Kinase and -tyrosine Phosphatase*

Hyaluronan (HA) is important for joint cavitation, lubrication, volume regulation and synovial fluid drainage but little is known about the regulation of joint HA synthesis/secretion in vivo....Full Text Available

2003-07-15

Regulation of Mixed Lineage Kinase 3 is Required for Neurofibromatosis-2-Mediated Growth Suppression in Human Cancer

We have used the two-electrode voltage clamp technique and the patch clamp technique to investigate the regulation of ROMK1 channels by protein-tyrosine phosphatase (PTP) and protein-tyrosine...Full Text Available

2001-03-09

Rapamycin inhibits trypanosome cell growth by preventing TOR complex 2 formation

The Neurofibromatosis-2 (NF2) tumor suppressor merlin negatively regulates cell proliferation in numerous cell types. We have previously shown that the NF2...Full Text Available

2011-02-17

PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast

Target of rapamycin (TOR) kinases control cell growth through two functionally distinct multiprotein complexes. TOR complex 1 (TORC1) controls temporal cell growth and is sensitive to rapamycin, whereas...Full Text Available

2008-09-23

Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer

Eukaryotic cells can massively transport their own cytoplasmic contents into a lytic compartment, the vacuole/lysosome, for recycling through a conserved system called autophagy. The key process in...Full Text Available

2011-01-01

PKC expression is regulated by dietary K intake and mediates internalization of SK channels in the CCD

Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available

2009-11-01

Oligomycin-induced Bioenergetic Adaptation in Cancer Cells with Heterogeneous Bioenergetic Organization

We have used Western blot analysis and immunocytochemistry to determine the effect of dietary K intake on the expression of protein kinase C (PKC) isoforms in the kidney. Western blot has demonstrated...Full Text Available

2004-06-01

Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling

Cancer cells constantly adapt to oxidative phosphorylation (OXPHOS) suppression resulting from hypoxia or mitochondria defects. Under the OXPHOS suppression, AMP-activated protein kinase (AMPK) regulates...Full Text Available

2010-04-23

Neurotensin Receptor 1 Is Expressed in Gastrointestinal Stromal Tumors but Not in Interstitial Cells of Cajal

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate...Full Text Available

2000-12-01

Lnk constrains myeloproliferative diseases in mice

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present...Full Text Available

H-1152 Effects on Intraocular Pressure and Trabecular Meshwork Morphology of Rat Eyes

Hematopoietic stem and progenitor cell (HSPC) expansion is regulated by intrinsic signaling pathways activated by cytokines. The intracellular kinase JAK2 plays an essential role in cytokine signaling,...Full Text Available

2010-06-01

Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis.

AbstractPurposeThe aim of this study was to elucidate the effects of the Rho-kinase inhibitor, H-1152, on cultured human trabecular meshwork (HTM) cells, TM morphology,...Full Text Available

2008-08-01

Effects of norepinephrine infusion on myocardial high-energy phosphate content and turnover in the living rat.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with a high incidence of colon cancer. Dysplasia is a precursor to carcinoma and a predictor of malignant potential; epithelia...Full Text Available

1994-02-01

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DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis

Using 31P-nuclear magnetic resonance, we studied the relationship between myocardial high-energy phosphate content and flux values for the creatine kinase reaction in the living rat under inotropic...Full Text Available

1987-06-01

Differential Regulation of Mitogen-Activated Protein Kinase Pathways by Acetaminophen and Its Nonhepatotoxic Regioisomer 3?-Hydroxyacetanilide in TAMH Cells

Exposure of Mycobacterium tuberculosis to hypoxia is known to alter the expression of many genes, including ones thought to be involved in latency, via the transcription factor DevR...Full Text Available

2007-08-01

DNA replication in vertebrates requires a homolog of the Cdc7 protein kinase

Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States....Full Text Available

2010-07-01

Cytokinin-Dependent Photorespiration and the Protection of Photosynthesis during Water Deficit1[W][OA

CDC7 is an essential gene required for DNA replication in Saccharomyces cerevisiae. Cdc7p homologs have recently been identified in vertebrates, but their role in DNA...Full Text Available

1999-03-16

Co-Induction of LTP and LTD and Its Regulation by Protein Kinases and Phosphatases

We investigated the effects of P_SARK∷IPT (for Senescence-Associated Receptor Kinase∷Isopentenyltransferase) expression and cytokinin production...Full Text Available

2009-07-01

Chemical activation of MEK1 - a redox trigger for evaluating the effects of phosphorylation.

The cellular properties of long-term potentiation (LTP) following pairing of pre- and postsynaptic activity were examined at a known glutamatergic synapse in the leech, specifically between the pressure...Full Text Available

2010-05-01

Calcium/Calmodulin-Dependent Protein Kinase II Mediates Hippocampal Glutamatergic Plasticity During Benzodiazepine Withdrawal

An approach to generate mimics of phosphorylated serine proteins chemically through site-specific sulfonation of cysteine is presented. This chemical modification is reversible in the presence of reducing agent and therefore is analogous to the kinase/phosphatase system used in nature. PMID:21717004

2011-06-30

Beyond AICA Riboside: In Search of New Specific AMP-activated Protein Kinase Activators

Benzodiazepine withdrawal anxiety is associated with potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal...Full Text Available

2010-08-01

Autophosphorylation Within the Atg1 Activation Loop Is Required for Both Kinase Activity and the Induction of Autophagy in Saccharomyces cerevisiae

Summary5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICA riboside) has been extensively used in vitro and in vivo to...Full Text Available

2009-01-01

ATM-Dependent Phosphorylation of ATF2 Is Required for the DNA Damage Response

Autophagy is an evolutionarily conserved degradative pathway that has been implicated in a number of physiological events important for human health. This process was originally identified as a response...Full Text Available

2010-07-01

AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model

SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available

2005-05-27

A Conserved Role for Phosphoinositide-3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

BackgroundObesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates...Full Text Available

?Activation of the mitogen-activated protein kinase pathways by heat shock

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1α and increased fatty acid oxidative (FAO) capacity. It is...Full Text Available

2007-10-01

Use of integrin-linked kinase to extend function of encapsulated pancreatic tissue

In addition to inducing new transcriptional activities that lead within a few hours to the accumulation of heat shock proteins (Hsps), heat shock activates within minutes the major signaling transduction...Full Text Available

2002-04-01

Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development

We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)

2010-12-15

Dietary turmeric modulates DMBA-induced p21ras, MAP kinases and AP-1/NF-?B pathway to alter cellular responses during hamster buccal pouch carcinogenesis

Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can ...

2003-11-27

British Library Electronic Table of Contents (United Kingdom)

The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12?weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished ...

2008-01-01

Tomato 14-3-3 Protein 7 Positively Regulates Immunity-Associated Programmed Cell Death by Enhancing Protein Abundance and Signaling Ability of MAPKKK ?^[C]^[W]

The direct interaction between ASH2, a Drosophila trithorax group protein, and SKTL, a nuclear phosphatidylinositol 4-phosphate 5-kinase, implies a role for phosphatidylinositol 4,5-bisphosphate in maintaining transcriptionally active chromatin.

Programmed cell death (PCD) is triggered when Pto, a Ser-Thr protein kinase, recognizes either the AvrPto or AvrPtoB effector from Pseudomonas syringae pv tomato. This...Full Text Available

2010-01-01

Targeting AMP-activated protein kinase in adipocytes to modulate obesity-related adipokine production associated with insulin resistance and breast cancer cell proliferation

The products of trithorax group (trxG) genes maintain active transcription of many important developmental regulatory genes, including homeotic genes. Several trxG proteins have been shown to act in...Full Text Available

2004-07-01

100

Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

BackgroundAdipokines, e.g. TNFα, IL-6 and leptin increase insulin resistance, and consequent hyperinsulinaemia influences breast cancer progression. Beside its mitogenic...Full Text Available

1 2 3 4 5 6 7 8 9 10

101

British Library Electronic Table of Contents (United Kingdom)

A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.

2009-01-01

102

Synergistic Activation of Glucose-6-Phosphate Dehydrogenase and NAD(P)H oxidase by Src kinase Elevates Superoxide in Type 2 Diabetic, Zucker fa/fa, Rat Liver

Selective Expression in Carotid Body Type I Cells of a Single Splice Variant of the Large Conductance Calcium- and Voltage-activated Potassium Channel Confers Regulation by AMP-activated Protein Kinase*

Glucose metabolism through glycolysis and hexosamine pathway has been shown to be altered in type 2 diabetes. However, its fate through the pentose phosphate pathway (PPP) is currently unclear....Full Text Available

2009-08-01

103

Scyl1 Facilitates Nuclear tRNA Export in Mammalian Cells by Acting at the Nuclear Pore Complex

Inhibition of large conductance calcium-activated potassium (BK_Ca) channels mediates, in part, oxygen sensing by carotid body type I cells. However, BK_Ca channels remain active...Full Text Available

2011-04-08

104

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

Scyl1 is an evolutionarily conserved N-terminal protein kinase-like domain protein that plays a role in COP1-mediated retrograde protein trafficking in mammalian cells. Furthermore, loss of Scyl1 function...Full Text Available

2010-07-15

105

Rapid inhibition of vasoconstriction in renal afferent arterioles by aldosterone

The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression....Full Text Available

2006-10-09

106

DEFF Research Database (Denmark)

Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse transcription-polymerase chain reaction and ...

2003-01-01

107

Primitive hematopoietic cells resist HIV-1 infection via p21^{Waf1/Cip1/Sdi1}

Overexpression of Partner of Numb Induces Asymmetric Distribution of the PI4P 5-Kinase Skittles in Mitotic Sensory Organ Precursor Cells in Drosophila

Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21^{Waf1/Cip1/Sdi1} (p21), a known regulator...Full Text Available

2007-02-01

108

Nucleotide sequence and genetic analysis of a 13.1-kilobase-pair Pseudomonas denitrificans DNA fragment containing five cob genes and identification of structural genes encoding Cob(I)alamin adenosyltransferase, cobyric acid synthase, and bifunctional cobinamide kinase-cobinamide phosphate guanylyltransferase.

Unequal segregation of cell fate determinants at mitosis is a conserved mechanism whereby cell fate diversity can be generated during development. In Drosophila, each sensory organ...Full Text Available

109

NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma

A 13.1-kb DNA fragment carrying Pseudomonas denitrificans cob genes has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment contained five different cob genes named...Full Text Available

1991-10-01

110

Mutational Analysis of the Carboxy-Terminal (YGX)₄ Repeat Domain of CpsD, an Autophosphorylating Tyrosine Kinase Required for Capsule Biosynthesis in Streptococcus pneumoniae

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The...Full Text Available

2011-02-15

111

Multistage skin tumor promotion: involvement of a protein kinase

In Streptococcus pneumoniae, CpsB, CpsC, and CpsD are essential for encapsulation, and mutants containing deletions of cpsB, cpsC, or cpsD...Full Text Available

2003-05-01

112

Mobilization of the genetically engineered plasmid pHSV106 from Escherichia coli HB101(pHSV106) to Enterobacter cloacae in drinking water.

Current information suggests that chemical carcinogenesis is a multistep process with one of the best studied models in this regard being the two-stage carcinogenesis system using mouse skin. The effects of several carcinogens and tumor promoters in various sequences of application were studied to examine the nature of the process. The actions of several tumor inhibitors were compared. (ACR)

1980-01-01

113

Mechano-transduction in Osteoblastic Cells Involves Strain-regulated Estrogen Receptor ?-mediated Control of Insulin-like Growth Factor (IGF) I Receptor Sensitivity to Ambient IGF, Leading to Phosphatidylinositol 3-Kinase/AKT-dependent Wnt/LRP5 Receptor-independent Activation of ?-Catenin Signaling*

We have used triparental matings to demonstrate transfer (mobilization) of the nonconjugative genetically engineered plasmid pHSV106, which contains the thymidine kinase gene of herpes simplex virus...Full Text Available

1991-01-01

114

Magnesium Sensitizes Slow Vacuolar Channels to Physiological Cytosolic Calcium and Inhibits Fast Vacuolar Channels in Fava Bean Guard Cell Vacuoles1

The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered....Full Text Available

2010-03-19

115

Isoform-Specific Functions of Phosphoinositide 3-Kinases: p110? but Not p110? Promotes Optimal Allergic Responses In Vivo1

Vacuolar ion channels in guard cells play important roles during stomatal movement and are regulated by many factors including Ca²⁺, calmodulin, protein kinases, and phosphatases....Full Text Available

1999-11-01

116

Involvement of protein kinase C in the mechanism of action of Escherichia coli heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205

The leukocyte-enriched p110γ and p110δ isoforms of PI3K have been shown to control in vitro degranulation of mast cells induced by cross-linking...Full Text Available

2008-02-15

117

Insulin-like growth factor II receptor is phosphorylated by a tyrosine kinase in adipocyte plasma membranes

The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP_3-mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKC#alpha#) was specified using isotype-specific ...

2005-08-01

118

Forkhead Box Transcription Factor FOXO3a Regulates Estrogen Receptor Alpha Expression and Is Repressed by the Her-2/neu/Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

Incorporation of /sup 32/P from (gamma-32P)ATP into tyrosine residues of the insulin-like growth factor (IGF)-II receptor was observed in a Triton X-100-insoluble fraction of rat adipocyte plasma membranes. IGF-II receptor phosphorylation proceeded to a stoichiometry of approximately 0.5 mol of phosphate/IGF-II binding site after 10 min of incubation at 4 degrees C. A Km for ATP of 6 microM was calculated for this phosphorylation reaction. Addition of IGF-II caused an approximately 2-fold increase in tyrosine phosphorylation of the IGF-II receptor in this preparation. In contrast, phosphorylation of angiotensin II by the Triton X-100 washed membranes was not stimulated by IGF-II. Incubation of purified receptor immobilized on IGF-II agarose or of receptor-enriched low density microsomal membranes with (gamma-32P)ATP did not result in appreciable incorporation of (/sup 32/P)phosphate into the IGF-II receptor nor into exogenous substrates. These data suggest that the IGF-II receptor is ...

1986-06-15

119

ERK-dependent and -independent pathways trigger human neural progenitor cell migration

The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factor receptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available

2004-10-01

120

Cordycepin Blocks Lung Injury-Associated Inflammation and Promotes BRCA1-Deficient Breast Cancer Cell Killing by Effectively Inhibiting PARP

Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, ...

2007-05-15

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121

Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27^kip1in rats

Cordycepin has been shown to interfere with a myriad of molecular processes from RNA elongation to kinase activity, and prevents numerous inflammatory processes in animal models. Here we show in a mouse...Full Text Available

2011-09-01

122

Alterations in Adenylate Kinase Activity in Human PBMCs after In Vitro Exposure to Electromagnetic Field: Comparison between Extremely Low Frequency Electromagnetic Field (ELF) and Therapeutic Application of a Musically Modulated Electromagnetic Field (TAMMEF)

BackgroundPulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27^kip1, one of critical cyclin-dependent kinase inhibitors, has been...Full Text Available

2010-01-01

123

Turnover of whole body proteins and myofibrillar proteins in middle-aged active men

This study investigated the effects of electromagnetic fields on enzymes involved in purine metabolism in human peripheral blood mononuclear cells in vitro. Cells were obtained from 20 volunteers. We...Full Text Available

2009-01-01

124

The Structure of the Amyloid-[beta] Peptide High-Affinity Copper II Binding Site in Alzheimer Disease

Endurance-trained older men have a higher proportion of lean tissue and greater muscle cell oxidative capacity, reversing age-related trends and suggesting major changes in protein metabolism. In this study, protein turnover was determined in 6 middle-aged (52+/-1 yr) men who were well trained (VO_2 max 55.2+/-5.0 ml O_2/kg.min) and lean (body fat 18.9+/-2.8%, muscle mass 36.6+/-0.6%). The maintained habitual exercise while consuming 0.6, 0.9 or 1.2 g protein/kg.day for 10-day periods. N flux was measured from "1"5N in urea after oral "1"5N-glycine administration. Myofibrillar protein breakdown was estimated from urinary 3-methyl-histidine. Dietary protein had no effect on turnover rates, even when N balance was negative. Whole body protein synthesis was 3.60+/-0.12 g/kg.day and breakdown was 3.40+/-0.14 g/kg.day for all N intakes. Whole body protein flux, synthesis and breakdown were similar to values reported for sedentary young (SY) or sedentary old (SO) men on ...

1986-04-13

125

Platinum(II) complexes as spectroscopic probes for biomolecules

Neurodegeneration observed in Alzheimer disease (AD) is believed to be related to the toxicity from reactive oxygen species (ROS) produced in the brain by the amyloid-{beta} (A{beta}) protein bound primarily to copper ions. The evidence for an oxidative stress role of A{beta}-Cu redox chemistry is still incomplete. Details of the copper binding site in A{beta} may be critical to the etiology of AD. Here we present the structure determined by combining x-ray absorption spectroscopy (XAS) and density functional theory analysis of A{beta} peptides complexed with Cu{sup 2+} in solution under a range of buffer conditions. Phosphate-buffered saline buffer salt (NaCl) concentration does not affect the high-affinity copper binding mode but alters the second coordination sphere. The XAS spectra for truncated and full-length A{beta}-Cu{sup 2+} peptides are similar. The novel distorted six-coordinated (3N3O) geometry around copper in the A{beta}-Cu{sup 2+} complexes include three ...

2008-11-03

126

Isoelectric focusing purity criteria and "1H NMR detectable spectroscopic heterogeneity in the major isolated monomer hemoglobins from Glycera dibranchiata

The use of platinum(II) complexes as tags and probes for biomolecules is indeed advantageous for their reactivities can be selective for certain purposes through an interplay of mild reaction conditions and of the ligands bound to the platinum. The use of {sup 195}Pt NMR as a method of detecting platinum and its interactions with biomolecules was carried out with the simplest model of platinum(II) tagging to proteins. Variable-temperature {sup 195}Pt NMR spectroscopy proved useful in studying the stereodynamics of complex thioethers like methionine. The complex, Pt(trpy)Cl{sup +}, with its chromophore has a greater potential for probing proteins. It is a noninvasive and selective tag for histidine and cysteine residues on the surface of cytochrome c at pH 5. The protein derivatives obtained are separable, and the tags are easily quantitated and differentiated through the metal-to-ligand charge transfer bands which are sensitive to the environment of the tag. ...

1990-09-21

127

Polyphenol rich botanicals used as food supplements interfere with EphA2-ephrinA1 system

Three major monomeric hemoglobins have been isolated from the erythrocytes of Glycera dibranchiata. Their importance to structure-function studies of heme proteins lies in the fact that they have been shown to possess an exceptional amino acid substitution. In these proteins, the E-7 position is occupied by leucine rather than the more common distal histidine. This substitution alters the polarity of the heme ligand binding environment compared to myoglobin. Due to this, the G. dibranchiata monomer hemoglobins are attracting much attention. However, until now no purity criterion has been developed. Here the authors demonstrate that, for all of the Glycera momomer hemoglobins, multiple line patterns are shown on high-voltage isoelectric focusing (IEF) gels. Most of these lines are shown to be a consequence of heme-related phenomena and can be understood on the basis of changes in oxidation and ligation state of the heme iron. The multiple line pattern does not ...

128

British Library Electronic Table of Contents (United Kingdom)

The Eph tyrosine kinase receptors and their ephrin ligands play a central role in several human cancers and their deregulated expression or function promotes tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE) have been recently found to inhibit Eph-kinase phosphorylation. In order to evaluate the potential contribution of edible and medicinal plants on EphA2-ephrinA1 modulation, 133 commercially available plant extracts used as food supplements, essential and fixed oils were screened with an ELISA-based binding assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in a dose-dependent manner (IC"5"0 0.83-24@mg/ml). Functional studies on PC3 prostate adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc-induced EphA2-pho...

2011-01-01

129

Phosphorylation of proteins in Clostridium thermohydrosulfuricum

Mechanism of adenylate kinase. Dose adenosine 5'-triphosphate bind to the adenosine 5'-monophosphate site

Cell extracts of the thermophile Clostridium thermohydrosulfuricum catalyzed the phosphorylation by (..gamma..-/sup 32/P)ATP of several endogenous proteins with M/sub r/s between 13,000 and 100,000. Serine and tyrosine were the main acceptors. Distinct substrate proteins were found in the soluble (e.g., proteins p66, p63, and p53 of M/sub r/s 66,000, 63,000, and 53,000, respectively) and particulate (p76 and p30) fractions, both of which contained protein kinase and phosphatase activity. The soluble fraction suppressed the phosphorylation of particulate proteins and contained a protein kinase inhibitor. Phosphorylation of p53 was promoted by 10..mu..M fructose 1,6-bisphosphate or glucose 1,6-bisphosphate and suppressed by hexose monophosphates, whereas p30 and p13 were suppressed by 5 ..mu..M brain (but not spinach) calmodulin. Polyamines, including the odd polyamines characteristic of thermophiles, modulated the labeling of most of the ...

1986-02-01

130

In vivo phosphorylation of histones H1 and H5 in calf thymus and chicken erythrocytes as studied by /sup 31/P nuclear magnetic resonance spectroscopy

Although the subtrate binding properties of adenylate kinase (AK) have been studied extensively by various biochemical and biophysical techniques, it remains controversial whether uncomplexed adenosine 5'-triphosphate (ATP) binds to the adenosine 5'-monophosphate (AMP) site of AK. The authors present two sets of experiments which argue against binding of ATP to the AMP site. (a) /sup 31/P nuclear magnetic resonance titration of ATP with AK indicated a 1:1 stoichiometry on the basis of changes in coupling constants and line widths. This ruled out binding of ATP to both sites. (b) ATP and MgATP were found to behave similarly by protecting AK from spontaneous inactivation while AMP showed only a small degree of protection. Such inactivation could also be protected or reversed by dithioerythritol and is most likely due to oxidation of sulfhydryl groups, one of which (cysteine-25) is located near the MgATP site. The results support binding of ATP to ...

1987-10-06

131

GROWTH REGULATION IN ROUS SARCOMA VIRUS INFECTED CHICKEN EMBRYO FIBROBLASTS: THE ROLE OF THE src GENE

The /sup 31/P NMR method was first applied to characterize in vivo phosphorylation of H1 and H5 in calf thymus and chicken erythrocytes as well as in vitro phosphorylation of H1 and H5 by cAMP-dependent protein kinase. The amino acid residues phosphorylated in vivo in the histones were exclusively serine residues, and the mole fraction of phosphoserine was estimated to be 0.34 and 0.27 per molecule of calf thymus H1 and chicken erythrocyte H5, respectively. Interestingly, chicken erythrocyte H1 was not phosphorylated in vivo. Three H1 subtypes from calf thymus H1 varied in the /sup 31/P NMR spectra, and the bisected fragments of calf thymus H1 and chicken erythrocyte H5 exhibited characteristic spectral patterns, indicating that there are considerable diversities of the degree of phosphorylation and phosphorylation sites in very-lysine-rich histones. Furthermore, it was found that the microenvironment of phosphoserine residues phosphorylated in vivo in calf thymus ...

1987-08-01

132

Cyclin-Dependent Kinase Inhibitor p16 and p21 Expression, and Cell Cycle Change in Human Lens Epithelial Cell Line SRA 01/04 following Contact Inhibition in Normal Culture

We report here a study of the mechanisms leading to loss of growth control in chicken embryo fibroblasts transformed by Rous sarcoma virus (RSV). We have been particularly concerned with the role of the src gene in this process, and have used RSV mutants temperature sensitive (ts) for transformation to investigate the nature of the growth regulatory lesion. The two principal findings were (1) the stationary phase of the cell cycle (G{sub 1}) in chick embryo fibroblasts seems to have two distinct regulatory compartments (using the terminology of Brooks et al. we refer to these as 'Q' and 'A' states). When rendered stationary at 41.5 C by serum deprivation, normal cells enter a Q state, but cells infected with the ts-mutant occupy an A state. (2) Whereas normal cells can occupy either state depending on culture conditions, the ts-infected cells, at 41.5 C, do not seem to enter Q even though a known src gene product, a kinase, is ...

1980-07-01

133

British Library Electronic Table of Contents (United Kingdom)

Abstract Purpose: To describe the pattern of expression of the cyclin-dependent kinase inhibitors (CDKIs) p16, p21 and p27, and the cell cycle in SRA 01/04 cells relative to contact inhibition. Methods: SRA 01/04 cells were grown to overconfluence under normal conditions. At various phases of the cell growth, cells were assayed by flow cytometry and Western blotting for the expression of CDKIs. Results: Expression of p16 was detected from early logarithmic growth to stationary phases, during which the number of cells in G0/G1 increased from 46 to 69%. Expression of p21 was detected only during the overgrowth phase, when 60% of the cells were in G0/G1. Expression of p27 was not observed in SRA 01/04 cells. Conclusions: p16 expression was likely mediated by G0/G1 arrest to induce contact inh...

2011-01-01

134

Changes in intracellular Ca2+ levels induced by cytokines and P2 agonists differentially modulate proliferation or commitment with macrophage differentiation in murine hematopoietic cells.

Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport

The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be ...

2008-09-05

135

DEFF Research Database (Denmark)

Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding ...

2006-01-01

136

The ATG1/ATG13 Protein Kinase Complex Is Both a Regulator and a Target of Autophagic Recycling in Arabidopsis.

Friend Spleen Focus-Forming Virus Activates the Tyrosine Kinase sf-Stk and the Transcription Factor PU.1 to Cause a Multi-Stage Erythroleukemia in Mice.

Autophagy is an intracellular recycling route in eukaryotes whereby organelles and cytoplasm are sequestered in vesicles, which are subsequently delivered to the vacuole for breakdown. The process is induced by various nutrient-responsive signaling cascades converging on the Autophagy-Related1 (ATG1)/ATG13 kinase complex. Here, we describe the ATG1/13 complex in Arabidopsis thaliana and show that it is both a regulator and a target of autophagy. Plants missing ATG13 are hypersensitive to nutrient limitations and senesce prematurely similar to mutants lacking other components of the ATG system. Synthesis of the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts, which are essential for autophagy, still occurs in ATG13-deficient plants, but the biogenesis of ATG8-decorated autophagic bodies does not, indicating that the complex regulates downstream events required for autophagosome enclosure and/or vacuolar delivery. Surprisingly, levels of the ATG1a and ATG13a ...

2011-10-01

137

Tungsten Effects on Phosphate-Dependent Biochemical Pathways are Species and Liver Cell Line Dependent

HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus ...

2010-10-11

138

British Library Electronic Table of Contents (United Kingdom)

Tungsten, in the form of tungstate, polymerizes with phosphate, and as extensive polymerization occurs, cellular phosphorylation and dephosphorylation reactions may be disrupted, resulting in negative effects on cellular functions. A series of studies were conducted to evaluate the effect of tungsten on several phosphate-dependent intracellular functions, including energy cycling (ATP), regulation of enzyme activity (cytosolic protein tyrosine kinase [cytPTK] and tyrosine phosphatase), and intracellular secondary messengers (cyclic adenosine monophosphate [cAMP]). Rat noncancerous hepatocyte (Clone-9), rat cancerous hepatocyte (H4IIE), and human cancerous hepatocyte (HepG2) cells were exposed to 1-1000 mg/l tungsten (in the form of sodium tungstate) for 24 h, lysed, and analyzed for the ab...

2010-01-01

139

Tissue-specific expression of Fgfr2b and Fgfr2c isoforms, Fgf10 and Fgf9 in the developing chick mandible

British Library Electronic Table of Contents (United Kingdom)

SummaryExperimental evidence has demonstrated the importance of FGF signalling in morphogenesis of the mandibular processes. FGFs transmit their signals through four tyrosine kinase transmembrane receptors (FGFRs). Alternative splicing in FGFRs including FGFR2 generates different isoforms that exhibit different ligand-specificities, exclusive tissue distributions and specific biological functions. Despite extensive information regarding the isoform-specific patterns of expression Fgfr2c and Fgfr2b during morphogenesis of many organs, a comparative analysis of these specific isoforms in the chick mandible has not been reported. To better understand the function of FGFR2 in mandibular morphogenesis, we have analysed the expression Fgfr2b, Fgfr2c and their putative ligands Fgf10 and Fgf9, in ...

2006-01-01

140

Submitochondrial distribution of cAMP in its incubation with rat liver mitochondria

Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure

When labeled cAMP is incubated with isolated mitochondria from rat liver, it penetrates not only through the outer membrane of the mitochondria but also into the mitoplasts, where it is accumulated chiefly in the matrix. Damage to the mitochondrial membrane by freezing-thawing promotes not an influx but an efflux of cAMP out of the mitoplasts. A substantial part of the labeled nucleotide in all the investigated submitochondrial fractions was identified as intact cAMP by the method of thin-layer chromatography. The transport of cAMP into the mitochondria can explain the activation of their functions by the hormones that activate cytoplasmic adenylate cyclase and by extramitochondrial (cytosol) cAMP, as well as the presence of cAMP-dependent protein kinase and cAMP-phosphodiesterase in the mitochondria.

1986-03-20

1 2 3 4 5 6 7 8 9 10

141

British Library Electronic Table of Contents (United Kingdom)

Hsp20, referred to as HspB6, is constitutively expressed in various tissues. Specifically, HspB6 is most highly expressed in different types of muscle including vascular, airway, colonic, bladder, and uterine smooth muscle; cardiac muscle; and skeletal muscle. It can be phosphorylated at Ser-16 by both cAMP- and cGMP-dependent protein kinases (PKA/PKG). Recently, Hsp20 and its phosphorylation have been implicated in multiple physiological and pathophysiological processes including smooth muscle relaxation, platelet aggregation, exercise training, myocardial infarction, atherosclerosis, insulin resistance and Alzheimer's disease. In the heart, key advances have been made in elucidating the significance of Hsp20 in contractile function and cardioprotection over the last decade. This mini-rev...

2011-01-01

142

Rapamycin (sirolimus) protects against hypoxic damage in primary heart cultures via Na^+/Ca^2^+ exchanger activation

British Library Electronic Table of Contents (United Kingdom)

Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...

2011-01-01

143

Metabolic and molecular stress responses of gilthead seam bream Sparus aurata during exposure to low ambient temperature: an analysis of mechanisms underlying the winter syndrome

British Library Electronic Table of Contents (United Kingdom)

The winter syndrome in the gilthead sea bream Sparus aurata indicates that the species is exposed to critically low temperatures in Mediterranean aquaculture in winter. The present study of metabolic patterns and molecular stress responses during cold exposure was carried out to investigate this ?disease?, in light of the recent concept of oxygen and capacity limited thermal tolerance. The metabolic profile of fuel oxidation was examined by determining the activities of the enzymes hexokinase (HK), aldolase (Ald), pyruvate kinase (PK), l-lactate dehydrogenase (l-LDH), citrate synthase (CS), malate dehydrogenase (MDH) and 3-hydroxyacyl CoA dehydrogenase (HOAD) in heart, red and white muscle after exposure to temperatures of 10, 14 and 18?C. Especially, the increase in LDH activity combined ...

2010-01-01

144

Mechanism of Dephosphorylation of the SR Protein ASF/SF2 by Protein Phosphatase 1

British Library Electronic Table of Contents (United Kingdom)

SR proteins are essential splicing factors whose function is controlled by multi-site phosphorylation of a C-terminal domain rich in arginine-serine repeats (RS domain). The protein kinase SRPK1 has been shown to polyphosphorylate the N-terminal portion of the RS domain (RS1) of the SR protein ASF/SF2, a modification that promotes nuclear entry of this splicing factor and engagement in splicing function. Later, dephosphorylation is required for maturation of the spliceosome and other RNA processing steps. While phosphates are attached to RS1 in a sequential manner by SRPK1, little is known about how they are removed. To investigate factors that control dephosphorylation, we monitored region-specific mapping of phosphorylation sites in ASF/SF2 as a function of the protein phosphatase PP1. W...

2010-01-01

145

Degradation of leucine zipper-positive isoform of MYPT1 may contribute to development of nitrate tolerance

British Library Electronic Table of Contents (United Kingdom)

Aims A depressed cGMP-dependent protein kinase (PKG) activity is implicated in nitrate tolerance. The present study determines whether the leucine zipper-positive (LZ+) isoform of myosin phosphatase target subunit 1 (MYPT1), a key target protein for PKG actions, is involved in the development of nitrate tolerance. Methods and results Nitrate tolerance in in vitro preparations was obtained by a 24 h incubation with nitroglycerin (NTG). Nitrate tolerance in in vivo preparations was obtained by subcutaneous injection of mice with NTG, and the aortas were used. Protein levels of total MYPT1, MYPT1 (LZ+), PP1Cd, myosin light chain (MLC), and phosphorylated MLC were determined by Western blot analysis. Isometric vessel tension was determined by an organ chamber technique. Protein levels of MYPT1...

2010-01-01

146

Decreased dendritic spine density and abnormal spine morphology in Fyn knockout mice

British Library Electronic Table of Contents (United Kingdom)

Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP), synapse formation, and learning and memory. Fyn is also implicated in dendritic spine formation both in vitro and in vivo. However, whether Fyn's regulation of dendritic spine formation is brain-region specific and age-dependent is unknown. In the present study, we systematically examined whether Fyn altered dendritic spine density and morphology in the cortex and hippocampus and if these effects were age-dependent. We found that Fyn knockout mice trended toward a decrease in dendritic spine density in cortical layers II/III, but not in the hippocampus, at 1month of age. Additionally, Fyn knockout mice had significantly decreased dendritic spine density in both the cortex and hippocampus at 3months and 1year, an...

2011-01-01

147

Cyclosporine metabolic side effects: association with the WNK4 system

British Library Electronic Table of Contents (United Kingdom)

Abstract Background- Cyclosporine is used for treatment of transplanted patients and for immune-mediated diseases. Cyclosporine is known to cause a combination of metabolic side effects including hypertension, hyperkalemia, hypercalciuria and hypomagnesemia. These side effects except for hypomagnesemia are the cardinal features of familial hyperkalemia and hypertension (FHHt), also called pseudohypoaldosteronism type II (PHA II). FHHt is caused by mutations in the kinases WNK1 and WNK4 resulting in an increase in renal Na-Cl cotransporter (NCC) apical distribution and function. Therefore, we studied whether cyclosporine-s metabolic side effects are mediated by WNK4 and NCC. Design- Sprague-Dawley (SD) rats were treated by cyclosporine 25-mg-kg-1 subcutaneously for 14-days. Blood pressure, ...

2011-01-01

148

BzpF is a CREB-like transcription factor that regulates spore maturation and stability in Dictyostelium

British Library Electronic Table of Contents (United Kingdom)

The cAMP response element-binding protein (CREB) is a highly conserved transcription factor that integrates signaling through the cAMP-dependent protein kinase A (PKA) in many eukaryotes. PKA plays a critical role in Dictyostelium development but no CREB homologue has been identified in this system. Here we show that Dictyostelium utilizes a CREB-like protein, BzpF, to integrate PKA signaling during late development. bzpF^- mutants produce compromised spores, which are extremely unstable and germination defective. Previously, we have found that BzpF binds the canonical CRE motif in vitro. In this paper, we determined the DNA binding specificity of BzpF using protein binding microarray (PBM) and showed that the motif with the highest specificity is a CRE-like sequence. BzpF is necessary to ...

2011-01-01

149

Accumulation, Activity and Localization of Cell Cycle Regulatory Proteins and the Chloroplast Division Protein FtsZ in the Alga Scenedesmus quadricauda under Inhibition of Nuclear DNA Replication

British Library Electronic Table of Contents (United Kingdom)

Synchronized cultures of the green alga Scenedesmus quadricauda were grown in the absence (untreated cultures) or in the presence (FdUrd-treated cultures) of 5-fluorodeoxyuridine, the specific inhibitor of nuclear DNA replication. The attainment of commitment points, at which the cells become committed to nuclear DNA replication, mitosis and cellular division, and the course of committed processes themselves were determined for cell cycle characterization. FdUrd-treated cultures showed nearly unaffected growth and attainment of the commitment points, while DNA replication(s), nuclear division(s) and protoplast fission(s) were blocked. Interestingly, the FdUrd-treated cells possessed a very high mitotic histone H1 kinase activity in the absence of any nuclear division(s). Compared with the ...

2008-01-01

150

Mechanism of enzyme-catalyzed phospho group transfer

Differential regulation of the biosynthesis of glucose transporters by the PI3-K and MAPK pathways of insulin signaling by treatment with novel compounds from Liriope platyphylla.

To understand more fully the mechanism of enzyme-catalyzed phospho group transfer, the stereochemical course at phosphorus of four enzymes has been determined. First, using adenosine (..gamma..-(S)-/sup 16/O, /sup 17/O, /sup 18/O)triphosphate as the substrate, the reaction catalyzed by creatine kinase has been found to proceed with overall inversion of configuration at phosphorus. Second, using adenosine (..beta..-(S)-/sup 16/O, /sup 17/O, /sup 18/O)diphosphate as the substrate, the reaction catalyzed by adenylate kinase has been found also to proceed with overall inversion. Third, the reaction catalyzed by phosphoenolpyruvate carboxylase has been studied using ((S/sub p/)-/sup 16/O, /sup 17/O)thiophospoenolpyruvate as the substrate in H/sub 2/ /sup 18/O. Fourth, using adenosine 5'-O-((..gamma..S/sub p/)-..beta gamma..-/sup 17/O,..gamma..-/sup 17/O,/sup 18/O)(3-thiotriphosphate) as the substrate, the reaction catalyzed by pyruvate ...

1986-01-01

151

Cysteinyl peptides of rabbit muscle pyruvate kinase labeled by the affinity label 8-((4-bromo-2,3-dioxobutyl)thio)adenosine 5 prime -triphosphate

The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in ...

2010-12-14

152

Characterization of the major phosphoprotein and its kinase on the surface of the rat adipocyte

The affinity label 8-((4-bromo-2,3-dioxobutyl)thio)adenosine 5{prime}-triphosphate (8-BDB-TA-5{prime}-TP) reacts covalently with rabbit muscle pyruvate kinase, incorporating 2 mol of reagent/mol of enzyme subunit upon complete inactivation. Protection against inactivation is provided by phosphoenolpyruvate, K{sup +}, and Mn{sup 2+} and only 1 mol of reagent/mol of subunit is incorporated. The authors have now identified the resultant modified residues. After reaction with 8-BDB-TA-5{prime}-TP at pH 7.0, modified enzyme was incubated with ({sup 3}H)NaBH{sub 4} to reduce the carbonyl groups of enzyme-bound 8-BDB-TA-5{prime}-TP and to introduce a radioactive tracer into the modified residues. Following carboxymethylation and digestion with trypsin, the radioactive peptides were separated on a phenylboronate agarose column followed by reverse-phase high-performance liquid chromatography in 0.1% trifluoroacetic acid with an acetonitrile gradient. Gas-phase sequencing ...

1990-03-13

153

Transforming growth factor-b induces nerve growth factor expression in pancreatic stellate cells by activation of the ALK-5 pathway

Intact rat fat cell exposed to 12.5 ..mu..M (..gamma..-32P)ATP incorporate label into specific proteins within minutes. By solubilizing the reaction mixture with SDS which bypasses the subcellular fractionation steps, the labeled proteins can be identified in autoradiographs of SDS-PAGE gels. The most prominently labeled protein has an M/sub r/ of 42,000. Localization of this component to the cell surface can be made on the basis of inhibition of phosphorylation by addition of a protein derived from the rat brain with protein kinase inhibitory property, susceptibility of the phosphorylated protein to the tryptic digestion, inhibition of phosphorylation of this protein after brief exposure to melittin. To rule out the possibility that the cell surface protein might be a mitochondrial contaminant from broken cells, /sup 32/Pi-labeled and (..gamma..-/sup 32/P)ATP-labeled cells were chromatographed on a rabbit anti-pyruvate dehydrogenase antibody-Sepharose 4B column. A ...

1986-12-01

154

British Library Electronic Table of Contents (United Kingdom)

Nerve growth factor (NGF), a survival factor for neurons enforces pain by sensitizing nociceptors. Also in the pancreas, NGF was associated with pain and it can stimulate the proliferation of pancreatic cancer cells. Hepatic stellate cells (HSC) respond to NGF with apoptosis. Transforming growth factor (TGF)-b, one of the strongest pro-fibrogenic activators of pancreatic stellate cells (PSC) induced NGF and its two receptors in an immortalized human cell line (ihPSC) and primary rat PSC (prPSC) as determined by RT-PCR, western blot, and immunofluorescence. In contrast to HSC, PSC expressed both NGF receptors, although p75NTR expression was weak in prPSC. In contrast to ihPSC TGF-b activated both Smad signaling cascades in prPSC. NGF secretion was diminished by the activin-like kinase (ALK)...

2009-01-01

155

Transforming growth factor-b induces CD44 cleavage that promotes migration of MDA-MB-435s cells through the up-regulation of membrane type 1-matrix metalloproteinase

British Library Electronic Table of Contents (United Kingdom)

CD44, a transmembrane receptor for hyaluronic acid, is implicated in various adhesion-dependent cellular processes, including cell migration, tumor cell metastasis and invasion. Recent studies demonstrated that CD44 expressed in cancer cells can be proteolytically cleaved at the ectodomain by membrane type 1-matrix metalloproteinase (MT1-MMP) to form soluble CD44 and that CD44 cleavage plays a critical role in cancer cell migration. Here, we show that transforming growth factor-b (TGF-b), a multifunctional cytokine involved in cell proliferation, differentiation, migration and pathological processes, induces MT1-MMP expression in MDA-MB-435s cells. TGF-b-induced MT1-MMP expression was blocked by the specific extracellular regulated kinase-1/2 (ERK1/2) inhibitor PD98059 and the specific pho...

2009-01-01

156

Salicylate Treatment Improves Age-Associated Vascular Endothelial Dysfunction: Potential Role of Nuclear Factor kB and Forkhead Box O Phosphorylation

British Library Electronic Table of Contents (United Kingdom)

We hypothesized that I kappa B kinase (IKK)-mediated nuclear factor kappa B and forkhead BoxO3a phosphorylation will be associated with age-related endothelial dysfunction. Endothelium-dependent dilation and aortic protein expression/phosphorylation were determined in young and old male B6D2F1 mice and old mice treated with the IKK inhibitor, salicylate. IKK activation was greater in old mice and was associated with greater nitrotyrosine and cytokines. Endothelium-dependent dilation, nitric oxide (NO), and endothelial NO synthase phosphorylation were lower in old mice. Endothelium-dependent dilation and NO bioavailability were restored by a superoxide dismutase mimetic. Nuclear factor kappa B and forkhead BoxO3a phosphorylation were greater in old and were associated with increased express...

2011-01-01

157

Proteomic Analysis of Proteins Secreted by HepG2 Cells Treated with Butyl Benzyl Phthalate

British Library Electronic Table of Contents (United Kingdom)

Proteomic changes in proteins secreted by human hepatocellular carcinomas (HepG2) cells exposed to butyl benzyl phthalate (BBP) were evaluated. HepG2 cells were treated with three different concentrations of BBP (0, 10, or 25 ?M) for 24 or 48 h. Following incubation, the cells were subjected to proteomic analysis using two different pI ranges (4-7 and 6-9) and large-size two-dimensional gel electrophoresis. Results showed resolution of a total of 2776 protein spots. Of these, 29, including 19 upregulated and 10 downregulated proteins, were identified by electrospray ionization-mass spectrometry-mass spectrometry (ESI-MS/MS). Among these, the identities of cystatin C, Rho guanine nucleotide dissociation inhibitor, gelsolin, DEK protein, Raf kinase inhibitory protein, triose phosphate ...

2010-01-01

158

Nuclear Targeting of Methyl-Recycling Enzymes in Arabidopsis thaliana Is Mediated by Specific Protein Interactions.

Mutations in cyr1 and pat1 reveal pheromone-induced G1 arrest in the fission yeast Schizosaccharomyces pombe

Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reactions, S-adenosylhomocysteine (SAH) that would otherwise competitively inhibit methyltransferase (MT) activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH (Gly(150)-Lys(190)) is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein interaction motifs. ADK ...

2011-10-01

159

DEFF Research Database (Denmark)

Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non-dividing cells. Here we overcome this problem by using two mutants that bypass the nutritional requirements and respond to the M-factor mating pheromone in rich medium. The first mutant lacks the cyr1 gene which encodes adenylate cyclase and these cells contain no measurable amounts of cAMP. When M-factor is added to a growing h+ cyr1- strain it causes a transient G1 arrest of cell division, transcription of mat1-Pm, and elongation of the cells to form shmoos. The second mutant contains the temperature-sensitive pat1-114 allele. At 30 degrees C this mutant was previously shown not only to bypass the nutritional signal but also to stop growing in a state derepressed for pheromone-controlled functions. We now report that an h+ pat1-114 strain ...

1994-01-01

160

Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model

British Library Electronic Table of Contents (United Kingdom)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...

2011-01-01

1 2 3 4 5 6 7 8 9 10

161

Internal medical therapy of gastrointestinal stroma tumors; Internistische Therapie gastrointestinaler Stromatumoren

Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules

Until recently no active treatment for advanced or metastatic gastrointestinal stroma tumors (GIST) was available. The tyrosine kinase inhibitor imatinib has revolutionized the treatment of this disease and the median overall survival now reaches 5 years. The standard dose of imatinib is 400 mg per day. Locally advanced GIST should be treated with systemic therapy prior to surgical resection. Imatinib was recently licensed for adjuvant therapy following complete surgical removal of GIST in patients with a significant risk of recurrence. (orig.) [German] Bis vor einigen Jahren existierte keine wirksame systemische Therapie fuer fortgeschrittene oder metastasierte gastrointestinale Stromatumoren (GIST). Der Tyrosinkinaseinhibitor Imatinib hat die Behandlung dieser Tumoren revolutioniert, die mediane Ueberlebenszeit liegt heute bei etwa 5 Jahren. Die Standarddosierung von Imatinib betraegt initial 400 mg/Tag. Lokal fortgeschrittene Tumoren werden primaer systemisch ...

2009-12-15

162

British Library Electronic Table of Contents (United Kingdom)

Purpose HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule ZHER2:342 is a small (7?kDa) affinity protein binding to HER2 with an affinity of 22?pM. The goal of this study was to evaluate the use of ((4-hydroxyphenyl)ethyl)maleimide (HPEM) for radioiodination of ZHER2:342 and to compare the targeting properties of monomeric and dimeric forms of ZHER2:342. Methods The biodistribution of different radioiodinated derivatives of ZHER2:342 was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of 125I-PIB-ZHER2:342 and site-specifically labelled 125I-HPEM-ZHER2:342-C were compared. Biodistributions of monomeric 131I-HPEM-ZHER2:342-C and dimeric 125I-HPEM-(ZHER2:342)2-C were evaluated using a paire...

2009-01-01

163

Increase in phorbol ester binding in liver microsomes after chronic administration of phenobarbital

Identification of protein phosphorylation sites within Ser/Thr-rich cluster domains using site-directed mutagenesis and hybrid linear quadrupole ion trap Fourier transform ion cyclotron resonance mass spectrometry

The effect of chronic administration of phenobarbital on the binding of phorbol-12,13-dibutyrate (({sup 3}H)PDBu), an activator of protein kinase C (PKC), was examined in rat liver microsomes. A significant increase in the number of binding sites was observed in microsomes of Fisher 344 rats. However, no change appeared in liver cytosol binding of PDBu. Consequently, a translocation process of PKC is unlikely. The increase in ({sup 3}H)PDBu binding in liver microsomes is significant 24 h. after one injection of phenobarbital and reaches its maximum in 2 days. In other strains of rats (ACI and lean Zucker), significant differences were found in the increase of ({sup 3}H)PDBu binding in microsomes. Fisher 344 were the most sensitive, lean Zucker rats, the least sensitive. Those results parallel the pentoxy-resorufin O demethylase activity in the microsomes of the same animals. EC{sub 50} values for inhibition of ({sup 3}H)PDBu binding by pentobarbital were determined ...

1991-03-15

164

British Library Electronic Table of Contents (United Kingdom)

We describe a method for the analysis of multi-site phosphorylation in serine/threonine (Ser/Thr)-rich protein sequences. Site-specific mutagenesis was used to introduce tryptic cleavage sites in the serine glutamine/threonine glutamine cluster domain (SCD) of the human checkpoint protein kinase (Chk2). The mutant proteins were shown to autophosphorylate on residues that are inducibly phosphorylated when mammalian cells are exposed to ionizing radiation (serine 33/35, serine 516, threonine 68 and threonine 432). Five Ser/Thr clusters within the SCD were flanked by arginine or lysine residues to produce tryptic peptides for nanospray liquid chromatography (nanoLC)/linear quadrupole ion trap Fourier transform ion cyclotron resonance mass spectrometry. Phosphorylation sites were assigned usin...

2007-01-01

165

Final report of the specific research. Investigations on the analysis of bio-protective factors against radiation. 1998-2000 FY (Research Group of NIRS)

Enhanced MALDI-TOF MS Analysis of Phosphopeptides Using an Optimized DHAP/DAHC Matrix

This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also given. (N.I.)

2002-03-01

166

Development of a novel mouse tk{sup +/-} embryonic stem cell line for use in mutagenicity studies

Selecting an appropriate matrix solution is one of the most effective means of increasing the ionization efficiency of phosphopeptides in matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In this study, we systematically assessed matrix combinations of 2, 6-dihydroxyacetophenone (DHAP) and diammonium hydrogen citrate (DAHC), and demonstrated that the low ratio DHAP/DAHC matrix was more effective in enhancing the ionization of phosphopeptides. Low femtomole level of phosphopeptides from the tryptic digests of ?-casein and ?-casein was readily detected by MALDI-TOF-MS in both positive and negative ion mode without desalination or phosphopeptide enrichment. Compared with the DHB/PA matrix, the optimized DHAP/DAHC matrix yielded superior sample homogeneity and higher phosphopeptide measurement sensitivity, particularly when multiple phosphorylated peptides were assessed. Finally, the DHAP/DAHC matrix was applied to identify phosphorylation sites ...

2010-01-01

167

A novel small-molecule inhibitor of NF-#kappa#B signaling

A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mouse model for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 figs., 1 tab.

1996-12-31

168

In vitro evaluation of herpes simplex virus type 1 thymidine kinase reporter system in dynamic studies of transcriptional gene regulation

The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by TNF#alpha# and a set of ...

2008-04-18

169

p73 protein regulates DNA damage repair.

The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were ...

2006-07-15

170

Tyrosine phosphorylation of a 66KD soluble protein and augmentation of lectin induced mitogenesis by DMSO in human T lymphocytes

Although the p53 tumor suppressor is relatively well characterized, much less is known about the functions of other members of the p53 family, p73 and p63. Here, we present evidence that in specific pathological conditions caused by exposure of normal cells to bile acids in acidic conditions, p73 protein plays the predominant role in the DNA damage response. These pathological conditions frequently occur during gastric reflux in the human esophagus and are associated with progression to esophageal adenocarcinoma. We found that despite strong DNA damage induced by bile acid exposure, only p73 (but not p53 and p63) is selectively activated in a c-Abl kinase-dependent manner. The activated p73 protein induces DNA damage repair. Using a human DNA repair PCR array, we identified multiple DNA repair genes affected by p73. Two glycosylases involved in base excision repair, SMUG1 and MUTYH, were characterized and found to be transcriptionally regulated by p73 in DNA damage ...

2011-09-01

171

The effect of phytic acid on the levels of blood glucose and some enzymes of carbohydrate and lipid metabolism.

The authors have demonstrated that induction of mitogenesis in human T lymphocytes is associated with the tyrosine phosphorylation of a 66KD soluble substrate-TPP 66. Since DMSO has been shown to be a non-specific stimulator of tyrosine protein kinases they have examined the effect of DMSO on both activation and tyrosine phosphorylation in human T cells. Human peripheral blood T lymphocytes were isolated by dextran sedimentation, Ficol/Paque centrifugation and nylon wool filtration. Phosphorylation was performed in cells incubated with ["3"2P] orthophosphate followed by DMSO for 30 min. TPP 66 was identified by 2-D PAGE, autoradiography, and HV electrophoresis of the hydrolyzed protein. Concentrations of DMSO from 1% to 50% induced the tyrosine phosphorylation of TPP 66 with maximal stimulation seen at 20%. DMSO alone did not activate the T cells (measured by ["3H] thymidine incorporation) when tested at high concentrations for 30 sec to 10 min. (longer incubations ...

1986-04-13

172

Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel.

In this study, six groups of rats were fed as follows: Groups 1 and 2 were fed formulated diets supplemented with zinc or without zinc respectively. Groups 3 and 4 were fed formulated diets supplemented with zinc plus phytic acid extracted from sweet potato (Ipomea batatas) or commercial phytic acid respectively. Groups 5 and 6 were fed formulated diets supplemented with phytic acid extract from sweet potato or commercial phytic acid respectively. The animals were fed for three weeks and then sacrificed The activities of key enzymes of carbohydrate and lipid metabolism as well as transaminases in the liver were determined. Blood glucose level was also assessed. Phytic acid extract consumption from sweet potato and commercial phytic acid plus zinc supplement lowered blood glucose levels. There was no significant change in the activity of 6-phosphogluconate dehydrogenase among the groups. Similarly, phytic acid supplementation showed no significant decrease in the activity of pyruvate ...

2005-03-01

173

Natriuretic peptides in vascular physiology and pathology.

Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput screen for identification of inhibitors of a human intestinal CaCC based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells after lentiviral infection with the yellow fluorescent halide-sensing protein YFP-H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2-aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to multiple calcium-elevating agonists, including thapsigargin, without inhibition of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis transmembrane conductance regulator chloride channels. These compounds also inhibited ...

2007-12-14

174

Molecular characterization of the Spirometra mansonoides genome: renaturation kinetics, methylation, and hybridization to human cDNA probes.

Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), and type C natriuretic peptide receptor ...

2008-01-01

175

Missense mutations in the growth hormone receptor dimerization region in Laron syndrome

High molecular weight DNA from pleroceroid larvae of the tapeworm Spirometra mansonoides was purified from isolated nuclei by conventional techniques. The DNA so isolated has a melting temperature (Tm) of 87 degrees C and a guanine plus cytosine (G/C) content of 44%. 5-Methyl cytosine could not be detected in plerocercoid DNA by HPLC analysis of DNA hydrolysates, by radiolabeling 5'-termini of MspI digests with polynucleotide kinase, or by comparing restriction patterns generated by MspI and HpaII. Renaturation kinetics demonstrated that the genome of S. mansonoides contains repetitive as well as single copy sequences and has a genome size estimated at approx. 1.6 X 10(9) bp. Hybridization was carried out between plerocercoid DNA and cDNAs for human beta-actin, alpha-tubulin and growth hormone (hGH). Rationale for this analysis was based on known homologies among actin and tubulin genes in numerous species and on apparent similarities between hGH and a plerocercoid ...

1990-06-21

176

Honokiol-mediated inhibition of PI3K/mTOR pathway: a potential strategy to overcome immunoresistance in glioma, breast, and prostate carcinoma without impacting T cell function.

Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the dimerization domain of the GH receptor. One of these mutations, D152H, ...

1994-09-01

177

Genome analysis of F. nucleatum sub spp vincentii and its comparison with the genome of F. nucleatum ATCC 25586.

Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not significantly impair T cell ...

178

Gene Repressive Activity of RIP140 Through Direct Interaction with CDK8.

We present the draft genome sequence and its analysis for Fusobacterium nucleatum sub spp. vincentii (FNV), and compare that genome with F. nucleatum ATCC 25586 (FN). A total of 441 FNV open reading frames (ORFs) with no orthologs in FN have been identified. Of these, 118 ORFs have no known function and are unique to FNV, whereas 323 ORFs have functional orthologs in other organisms. In addition to the excretion of butyrate, H2S and ammonia-like FN, FNV has the additional capability to excrete lactate and aminobutyrate. Unlike FN, FNV is likely to incorporate galactopyranose, galacturonate, and sialic acid into its O-antigen. It appears to transport ferrous iron by an anaerobic ferrous transporter. Genes for eukaryotic type serine/threonine kinase and phosphatase, transpeptidase E-transglycosylase Pbp1A are found in FNV but not in FN. Unique ABC transporters, cryptic phages, and three types of restriction-modification systems have been identified in FNV. ORFs for ...

2003-06-01

179

Expression and function of fibroblast growth factor (FGF) 9 in hepatic stellate cells and its role in toxic liver injury

Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) recruitment during the T(3)-repressive phase. We also uncover direct interaction of RIP140 with ...

2011-08-25

180

Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle.

Hepatic injury and regeneration of the liver are associated with activation of hepatic stellate cells (HSC). Fibroblast growth factors (FGFs) and their receptors are important regulators of repair in various tissues. HSC express FGFR3IIIc as well as FGFGR4 and different spliced FGFR1IIIc and FGFR2IIIc isoforms which differ in the presence or absence of the acid box and of the first Ig-like domain. Expression of FGF9, known to be capable to activate the HSC FGFR2/3-isoforms, was increased in HSC in liver slice cultures after exposition to carbon tetrachloride, as an acute liver injury model. FGF9 significantly stimulated 3-H thymidine incorporation of hepatocytes, but failed to induce DNA synthesis in HSC despite the fact that FGF9 induced a sustained activation of extracellular signal-related kinases (ERK) 1/2. FGF9 induced an increased phosphorylation of Tyr436 of the fibroblast growth factor receptor substrate (FRS) 2, while phosphorylation of Tyr196 which is ...

2007-09-21

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181

A human breast cell model of pre-invasive to invasive transition

We previously reported that the peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) mRNA in rat epitrochlearis muscle was increased after swimming exercise training. In the present study, we demonstrated further that PGC-1 mRNA expression in the epitrochlearis muscle of 4-5-week-old male Sprague-Dawley rats was increased after a 6-h acute bout of low-intensity swimming exercise. With this increase, the expression level was approximately 8-fold of control and immersion group rats that stayed for 6-h in warm water, maintained at the identical temperature of the swimming barrel (35 degrees C) (p<0.01). Second, PGC-1 mRNA expression in the muscle was found to have increased 6-h after 30 10-s tetani contractions were induced by in vitro electrical stimulation. Finally, PGC-1 mRNA expression in the muscle incubated for 18-h with 0.5mM 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR: a 5' AMP-activated protein kinase (AMPK) activator) was ...

2002-08-16

182

Disruption of contact inhibition in rat liver epithelial cells by various types of AhR ligands

A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with ...

2008-03-10

183

Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model

The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell ...

2004-09-15

184