UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

BackgroundABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting...Full Text Available

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 ...

UK PubMed Central (United Kingdom)

The bovine syncytial virus, a member of the retroviral subfamily Spumavirinae, causes a persistent, asymptomatic infection in cattle. Nucleotide sequence analysis of the viral genome revealed two overlapping...Full Text Available

Science.gov (United States)

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 ...

Science.gov (United States)

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 ...

Energy Technology Data Exchange (ETDEWEB)

The DNA sequence motif ATTTGCAT (octamer) or its inverse complement has been identified as an evolutionarily conserved element in the promoter region of immunoglobulin genes. Two major DNA-binding proteins that bind in a sequence-specific manner to the octamer DNA sequence have been identified in mammalian species--a ubiquitously expressed protein (Oct-1) and a lymphoid-specific protein (Oct-2). During characterization of the promoter region of the chicken immunoglobulin light chain gene, the authors identified two homologous octamer-binding proteins in chicken B cells. when the cloning of the human gene for Oct-2 revealed it to be a member of a distinct family of homeobox genes, they sought to determine if the human Oct-2 cDNA could be used to identify homologous chicken homeobox genes. Using a human Oct-2 homeobox-specific DNA probe, they were able to identify 6-10 homeobox-containing genes in the chicken genome, demonstrating that the Oct-2-related subfamily of ...

CERN Document Server

2009 has been an extraordinary year for gamma-ray pulsar astronomy and 2010 promises to be equally good. Not only have we registered an extraordinary increase in the number of pulsars detected in gamma rays, but we have also witnessed the birth of new sub-families: first of all, the radio-quiet gamma pulsars and later an ever growing number of millisecond pulsars, a real surprise. We started with a sample of 7 gamma-ray emitting neutron stars (6 radio pulsars and Geminga) and now the Fermi-LAT harvest encompasses 24 "Geminga-like" new gamma-ray pulsars, a dozen millisecond pulsars and about thirty radio pulsars. Moreover, radio searches targeted to LAT unidentified sources yielded 18 new radio millisecond pulsars, several of which have been already detected also in gamma rays. Thus, currently the family of gamma-ray emitting neutron stars seems to be evenly divided between classical radio pulsars, millisecond pulsars and radio quiet neutron stars.

Energy Technology Data Exchange (ETDEWEB)

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a {lambda}gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu{sup 160}{yields}His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a {lambda}{sub max} at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former ...

Science.gov (United States)

A series of radioactive catastrophes (from 1948 to 1967) in the Southern Urals in the USSR led to intensive environmental contamination. Radioactive wastes were dispersed over the 20000 km(2) territory of four provinces-Chelyabinsk, Sverdlovsk, Tyumen' and Kurgan-due to the activity of the military facility that was built in 1948 for the production of nuclear bomb plutonium. The results of 50 years of investigations into the consequences of these disasters allow a general picture of the events that occurred to be reconstructed and allow the medical consequences of the irradiation of about half a million residents to be depicted. However, due to the atmosphere of secrecy and inadequate medical procedures, the results of medical studies of radiation victims are scant. The current protocols present a unique opportunity to study the DNA damage at the nucleotide resolution level in the genome of inhabitants of the given region, who presumably received chronic doses of irradiation. Studies ...