Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein phosphorylation catalysed by rat brain protein kinase C (PKC) has been studied in nuclei isolated from normal and regenerating rat liver. Histone H1 and a 40,000 molecular weight protein were hyperphosphorylated at all the explored regeneration times, ranging from 3 to 22 h after partial hepatectomy. Phosphorylation of the two substrates was totally dependent on calcium and lipids and was abolished by low concentration of staurosporine. The observed early change of phosphate content of histone H1 and of the 40,000 molecular weight protein on the time scale of liver regeneration suggests that PKC might be involved in the initial nuclear events leading to cell proliferation.
 ...
PMID:Increased phosphorylation of nuclear substrates for rat brain protein kinase C in regenerating rat liver nuclei. 151 Aug 79

Sphingomyelin (SM) and cholesterol are major lipid species of apical membranes in renal proximal tubular cells and confer to these membranes a low fluidity. Changes in membrane fluidity and/or lipidic composition were shown to affect the activity of cotransport systems of renal apical membranes. We evaluated the effect of decreasing membrane SM content on lipidic composition, membrane fluidity and sodium (Na)coupled uptakes in rabbit proximal tubular cells in primary culture. Sphingomyelinase (SMase) (30 to 250 mU/ml) decreased [3H]choline-labeled SM content, decreased cholesterol content, and increased cholesterol esterification. SMase did not modify membrane fluidity on isolated brush border membranes. SMase decreased Vmax of Na-dependent uptake of phosphate and alpha-methyl-D-glucoside, but not of alanine. SMase did not influence protein kinase C-induced inhibition of phosphate and glucose uptake. Increasing membrane cholesterol content with cholesterol-enriched liposomes subsequently to SMase action restored in part glucose uptake, but not phosphate uptake. In conclusion, SM degradation affected Na-phosphate and Na-glucose cotransports through changes in both SM and cholesterol contents of apical proximal membranes; these changes seemed to occur independently from changes in bulk membrane fluidity. These results suggest that SM and cholesterol have distinct and intricated roles in accessibility and/or activity of apical cotransport systems.
 ...
PMID:Sphingomyelin and cholesterol modulate sodium coupled uptakes in proximal tubular cells. 151 19

An extract of rat retina was subjected to Mono Q followed by chromatography on hydroxyapatite, and the protein kinase C (PKC) subspecies were identified by immunoblot and biochemical analysis. It was found that, although the relative activities assayed with myelin basic protein as a common phosphate acceptor vary greatly with one another, the alpha-, beta I-, beta II-, gamma-, delta-, epsilon-, zeta-, and another structurally unknown PKC subspecies are expressed in this tissue. Thus, the retina is a unique tissue which expresses most of the PKC subspecies so far identified in mammals.
 ...
PMID:Expression of protein kinase C subspecies in rat retina. 151 18

XLH (X-linked hypophosphataemia, gene symbol HYP, McKusick 307800, 307810) and its murine counterparts (Hyp and Gy) map to a conserved segment on the X-chromosome (Xp 22.31-p.21.3, human; distal X, mouse). Gene dosage has received relatively little attention in the long history of research on this disease, which began over 50 years ago. Bone and teeth are sites of the principal disease manifestations in XLH (rickets, osteomalacia, interglobular dentin). Newer measures of quantitative XLH phenotypes reveal gene dose effects in bone and teeth with heterozygous values distributed between those in mutant hemizygotes and normal homozygotes. On the other hand, serum phosphate concentrations (which are low in the mutant phenotype and thereby contribute to bone and tooth phenotypes) do not show gene dosage. In Hyp mice serum values in mutant hemizygotes, mutant homozygotes and heterozygotes are similar. Phosphate homeostasis reflects its renal conservation. Renal absorption of phosphate on a high-affinity, Na+ ion-gradient coupled system in renal brush border membrane is impaired and gene dosage is absent at this level; the mutant phenotype is fully dominant. Synthesis and degradation of 1,25(OH)2D are also abnormal in XLH (and Hyp), but gene dosage in these parameters has not yet been measured. An (unidentified) inhibitory trans-acting product of the X-linked locus, affecting phosphate transport and vitamin D metabolism, acting perhaps through cytosolic protein kinase C, could explain the renal phenotype. But why would it have a normal gene dose effect in bone and teeth? Since the locus may have duplicated (to form Hyp and Gy), and shows evidence of variable expression in different organs (inner ear, bone/teeth, kidney), it may have been recruited during evolution to multiple functions.
 ...
PMID:X-linked hypophosphataemia: a homologous phenotype in humans and mice with unusual organ-specific gene dosage. 152 20

Purified type II (beta) and type III (alpha) protein kinase C phosphorylates highly purified polyADP-ribose polymerase in vitro whereby 2 mols of phosphate are transferred from ATP to serine and threonine residues present in the 36 and 56 kDa polypeptide domains of the polymerase protein. Calf thymus DNA was a non-competitive inhibitor of the protein kinase C catalyzed phosphorylation of polyADP-ribose polymerase. Coincidental with the phosphorylation of the protein the polymerase activity and DNA binding capacity of polyADP-ribose polymerase were inhibited. These in vitro findings may have possible cell biological significance in cellular signal transduction.
 ...
PMID:Inhibition of DNA binding by the phosphorylation of poly ADP-ribose polymerase protein catalysed by protein kinase C. 153 Jun 31

The binding of agonistic monoclonal antibodies (mAb) to the CD3 antigen in T cells induces a rapid increase in tyrosine phosphorylation, inositive phosphate (IP) production, a rise in intracellular calcium and protein kinase C (PKC) activation. These intracellular signals have been implicated in the control of interleukin-2 and interleukin-2R receptor gene expression, thereby regulating T cell proliferation. Previous studies have shown that co-ligation of the CD45 and CD3 antigens inhibits CD3-induced tyrosine phosphorylation, IP production, calcium signals and T cell proliferation. It has therefore been suggested that the CD45 antigen uncouples the T cell receptor (TcR) from mitogenic signal pathways. In this study co-ligation of the CD3 and CD45 antigens with precisely constructed bispecific mAb did not inhibit CD3-induced T cell proliferation, IP production, calcium signals, diacylglycerol production or PKC activation. Furthermore, co-ligation of CD3 and CD45 antigens already cross-linked with IgM mAb did not lead to inhibition of CD3-induced calcium signals. Inhibitions of CD3-induced intracellular signals were observed following co-ligation of IgG CD45 and CD3 mAb with anti-IgG (F(ab')2 fragments. However, comparable inhibitions were also noted following co-ligation of CD3 with other abundant cell-surface antigens such as CD5 and LFA-1, and inhibitions were only observed when the CD3 mAb used required cross-linking to induce signals. These results suggested that the inhibitory effects of CD45 IgG mAb were not specific and were caused by the prevention of CD3-CD3 cross-linking following CD3 antigen co-ligation with other cell surface molecules. These findings are inconsistent with a specific inhibitory role for the CD45 phosphotyrosine phosphatase in uncoupling the TcR from mitogenic signal pathways.
 ...
PMID:Does co-aggregation of the CD45 and CD3 antigens inhibit T cell antigen receptor complex-mediated activation of phospholipase C and protein kinase C? 153 59

GAP-43 is a neuronal calmodulin-binding phosphoprotein that is concentrated in growth cones and presynaptic terminals. By sequencing tryptic and endoproteinase Asp-N phosphopeptides and directly determining the release of radioactive phosphate, we have identified three sites (serines 41 and 96 and threonine 172) that are phosphorylated, both in cultured neurons and in neonatal rat brain. These three sites account for most of the 32PO4 that was incorporated into GAP-43 in cultured neurons; 8-15% of each site was occupied with phosphate in GAP-43 isolated from neonatal rat brain. Phosphorylation of serine 41 in cultured neurons was stimulated by phorbol ester, indicating that it is the only site phosphorylated by protein kinase C. The resemblance of the sequence surrounding the other two sites suggests that they may be substrates for the same protein kinase. None of the sites phosphorylated by casein kinase II in vitro was phosphorylated in living cells or in neonatal rat brain. These results show that GAP-43 is a substrate for at least one protein kinase in addition to protein kinase C in living cells and brain.
 ...
PMID:GAP-43, a protein associated with axon growth, is phosphorylated at three sites in cultured neurons and rat brain. 153 24

A cytosolic insulin-sensitive serine kinase has been purified to apparent homogeneity in parallel from livers of control or acutely insulin-treated rats. The kinase is labile and requires rapid purification for stability. The kinase migrates as a band of apparent Mr = 90,000 on denaturing gels and elutes as a monomer on Superose 12 gel filtration. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis and renaturation, the 90-kDa band presumed to be the kinase shows kinase activity toward myelin basic protein in situ. Substrates of the kinase include Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide), ribosomal protein S6, S6 peptide, a proline-rich peptide substrate, microtubule-associated protein 2, and myelin basic protein. The kinase also phosphorylates histones H1 and H2B, but does not autophosphorylate to a significant stoichiometry. The activity of the kinase is inhibited by fluoride, glycerophosphate, p-nitrophenyl phosphate, p-nitrophenol, heparin, quercetin, poly-L-lysine, and potassium phosphate, but is unaffected by calcium, cAMP, spermine, protein kinase inhibitor peptide, phorbol myristate acetate, calcium plus phosphatidylserine, or vanadate. The kinase will utilize magnesium (10 mM) as well as manganese (1 mM) as a cofactor for maximal phosphotransferase activity. The kinase is not detected by immunoblotting with antibodies directed against protein kinase C or type II S6 kinase. Taken together, these properties distinguish this kinase from other insulin-sensitive kinases that have been described previously. The purified kinase from livers of insulin-treated rats shows a 5-20-fold higher specific activity compared to enzyme prepared from control rats, suggesting a covalent modification as the mechanism of activation. Incubation of purified, insulin-stimulated kinase with purified phosphatase 2A leads to deactivation of the kinase activity, and the phosphatase inhibitor nitrophenyl phosphate blocks this deactivation. The insulin-activated kinase fails to immunoblot with anti-tyrosine phosphate antibodies. Taken together, these results indicate that insulin activates this novel cytosolic protein kinase by a mechanism that causes its phosphorylation on serine or threonine residues.
 ...
PMID:Purification and characterization of a cytosolic insulin-stimulated serine kinase from rat liver. 153 38

Extracellular signal-regulated kinases (ERK) 1 and 2 are growth factor- and cytokine-sensitive serine/threonine kinases that are known to phosphorylate microtubule-associated protein 2 and myelin basic protein. The current studies examined whether ERK1 and/or ERK2 was present in T cells and whether they were phosphorylated and activated as a consequence of T cell activation. The data demonstrated that both ERK1 and ERK2 were present in Jurkat cells and peripheral blood T cells. In T cells, ERK2 was more prevalent than ERK1. The concentrations of ERK1 and ERK2 were not altered by stimulating the cells for 16 h with immobilized anti-CD3 mAb or anti-CD3 mAb and phorbol myristate acetate. mAb to CD3 and phorbol myristate acetate stimulated an increase in ERK1 and ERK2 MBP kinase activity. Anti-CD3 mAb triggered an increase their phosphate content which was detectable at 2 min but reached a maximum at 5 min. A portion of the increase in phosphate was caused by an increase in phosphotyrosine. We also examined the rate of ERK2 degradation. ERK2 was stable for up to 36 h, and its degradation was unaffected by the activation state of the cells. The data demonstrate that ERK1 and ERK2 are part of an anti-CD3 mAb-stimulated signal transduction cascade that is downstream of protein kinase C and, therefore, suggest that these kinases play an important role in T cell activation.
 ...
PMID:Extracellular signal-regulated kinases in T cells. Anti-CD3 and 4 beta-phorbol 12-myristate 13-acetate-induced phosphorylation and activation. 153 54

The protein B-50 (F1, GAP-43) is a presynaptic-specific substrate of protein kinase C, functionally related to neurotransmitter release. An increase in phosphorylation of this protein has been proposed as a molecular mechanism underlying long-term potentiation (LTP). B-50 phosphorylation measured by quantitative immunoprecipitation in rat hippocampal slices incubated in the presence of radiolabeled inorganic phosphate was increased for at least 1 hr after the induction of LTP in the CA1 region. No significant changes in B-50 phosphorylation were observed in untetanized slices stimulated at low frequency. The direct demonstration of an increased phosphorylation of the protein B-50 during LTP is consistent with the hypothesis that presynaptic mechanisms contribute to maintenance of LTP.
 ...
PMID:Phosphorylation of the presynaptic protein B-50 (GAP-43) is increased during electrically induced long-term potentiation. 153 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>