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

Xenopus oocytes are stimulated to undergo meiotic cell division in response to several types of mitogenic stimuli. Agents that reduce cAMP levels induce cell division in oocytes, and this occurs due to inhibition of adenylate cyclase with progesterone as well as by activation of phosphodiesterase with insulin. Phorbol esters and microinjected protein kinase C also promote cell division, implicating phospholipid breakdown as another signalling pathway competent to induce proliferation in this system. A third signalling pathway is via the tyrosine kinase activity of the insulin receptor. A proximal activation of a ribosomal protein S6 kinase by insulin has provided insight into the regulation of this pathway. All three of these signal transduction pathways lead to the activation of a cytoplasmic protein able to induce nuclear breakdown, chromosome condensation and spindle formation in vivo and in vitro. This protein, known as maturation-promoting factor, is associated with changes in protein phosphorylation on both serine and tyrosine residues. These results support a model in which signal transduction by different pathways activates a common cell cycle control element that regulates the G2----M transition via changes in protein phosphorylation.
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PMID:Mitogenic signalling and protein phosphorylation in Xenopus oocytes. 283 Dec 61

The addition of IL 2 to Con A-activated splenic T cells induced the rapid and time-dependent phosphorylation of membrane proteins with m.w. of 115,000 to 105,000, 90,000, and 66,000, and to a lesser extent 55,000 to 58,000, 40,000, and 34,000. Immunoprecipitations conducted with an anti-IL 2 receptor antibody indicated that the murine IL 2 receptor (55,000 to 58,000) was included in the set of IL 2-dependent phosphoproteins. Phosphorylation of these same proteins was also seen after IL 2 treatment of PHA-activated T cells and of the IL 2-dependent line CTLL-2. Membrane phosphorylation was dependent on physiologically relevant IL 2 concentrations (0.2 to 1 ng/ml), and was detected as early as 1 min after IL 2 addition, with maximal levels of phosphorylation achieved by 15 min. In contrast to these observations, the pattern of cytoplasmic protein phosphorylation remained unchanged after IL 2 addition, although IL 2 did augment the level of preexisting cytoplasmic phosphorylation induced by lectin. The pattern of membrane protein phosphorylation induced by IL 2 also overlapped in part with that induced after stimulation of Con A-activated T cells with the phorbol ester PMA. IL 2-stimulated phosphorylation was inhibited by the addition of agents that both stimulate cyclic AMP-dependent protein kinases and block lymphocyte mitogenesis. No effect was seen upon addition of agents that enhance cyclic GMP-dependent protein kinases. These observations support a role for specific membrane as opposed to cytoplasmic protein phosphorylation in the regulation of lymphocyte growth by IL 2, and also suggest that protein kinase A, and perhaps protein kinase C, participate as regulators of the IL 2 signaling mechanism.
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PMID:Interleukin 2-dependent phosphorylation of interleukin 2 receptors and other T cell membrane proteins. 300 13

The biochemical events initiated by mitogen in T lymphocytes are the subject of this paper. Following interaction of the mitogen with its receptors, a transmembrane 'trigger-type' signal is propagated which has both positive and negative correlates. The negative signal occurs with high mitogen concentrations and is associated with membrane freezing, microtubular aggregation, receptor capping, adenylate cyclase activation, and cellular cyclic AMP increases. The positive signal occurs with optimal mitogen concentrations and is associated with changes in membrane permeability and transport with influx of calcium and potassium ion and efflux of sodium, in transport processes for glucose, amino acids, and nucleosides, and in a collected series of early membrane lipid changes which can be considered essential for the positive signal. These lipid changes include the uptake of arachidonic acid and other fatty acids, choline, phosphate and other molecules, their incorporation into membrane phospholipids, particularly phosphatidylinositol (PI), and a turnover of PI with the production of inositol triphosphate, which can be related to calcium mobilization and diacylglycerol which activates a cytoplasmic protein kinase C. A key event associated with mitogen action is arachidonic acid release. Arachidonic acid may give rise to prostaglandins and thromboxanes as part of negative components of the signal through effects on the adenylate cyclase/cyclic AMP system. Arachidonic acid gives rise to eicosanoids like 5-, 11-, possibly 12- and 15-hydroxyperoxy and hydroxy eicosatetraenoic acids and leukotrienes B4 and C4. The activation of the 5-lipoxygenase, a critical calcium-dependent step, leads via the production of 5-HPETE and 5-HETE to the activation of membrane and soluble guanylate cyclase and the production of cyclic GMP. Cyclic GMP appears to be essential for mitogen activation and is associated with cyclic GMP-dependent protein kinase activation and the phosphorylation of a number of substrates. Calcium ion influx is clearly central to mitogen action. Calcium through its influx and mobilization from cellular stores is thought to contribute directly and indirectly through the action of calmodulin and protein kinase C to the activation of a number of enzymatic processes involved in the positive signal including phospholipase C, diglyceride kinase and lipase, 5-lipoxygenase, and guanylate cyclase. Cyclic GMP and calcium ion both participate in nuclear processes leading to RNA and protein synthesis. Interleukin 2 is associated with midcycle increases in cyclic GMP and entry into DNA synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transduction of signals in the activation of T lymphocytes: relation to leukemia. 304 Mar 20

Many cytoplasmic proteins, including Ca2+- and phospholipid-dependent protein kinase (protein kinase C) of polymorphonuclear leukocytes (PMNs) associate in Ca2+-dependent manner with phospholipid liposomes containing cardiolipin (CL), as in the case of phosphatidylserine (PS)-containing liposomes. A crude protein kinase C fraction was purified by association of the enzyme with CL-containing liposomes (flotation method). The partially purified protein kinase C from rat brain or guinea pig PMN was activated by the CL-containing liposomes in the presence of dioleoylglycerol (DG) and Ca2+. This activation was analogous to that of PS. The half maximum activity was obtained with 20 microM CL in the presence of 1 microM Ca2+ and 5 microM DG. Many of the cytoplasmic proteins which associate with CL-containing liposomes were preferentially phosphorylated by membrane-associated protein kinase C in the presence of DG and Ca2+. These results suggest that the association of cytoplasmic protein kinase C with the membrane has an important role in regulation of protein kinase C activity in relation to the association of other cytoplasmic proteins to the membrane.
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PMID:Activation of protein kinase C with cardiolipin-containing liposomes in relation to membrane-protein interaction. 362 65

Basic fibroblast growth factor (bFGF) was found to protect bovine aortic endothelial cells against the lethal effects of ionizing radiation by inhibiting the programmed cell death (apoptosis) induced in these cells by radiation exposure. The involvement of the bFGF receptor tyrosine kinase in this function was demonstrated by abrogation of the radioprotective effect of bFGF by a specific inhibitor of the bFGF receptor tyrosine kinase, the tyrphostin AG213. The downstream signaling after stimulation of the bFGF receptor tyrosine kinase in bovine aortic endothelial cells involved translocation of the alpha isotype of cytoplasmic protein kinase C (PKC) into the membrane and its activation within 30 s after bFGF stimulation. The involvement of PKC in the radioprotective effect conferred by bFGF was suggested by the demonstration that nonspecific PKC activation by short-term exposure (30 min) to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA; 30 ng/ml) mimicked the radioprotective effect of bFGF. Furthermore, treatment of the cells with the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (20 microM) abrogated the radioprotective effect of bFGF, as was observed after the depletion of cellular PKC by overnight preincubation with high-dose TPA (200 nM). Agarose gel electrophoresis of DNA extracted from irradiated bovine aortic endothelial cells showed that both TPA (30 ng/ml; 30 min) and bFGF (1 ng/ml) inhibited the apoptotic degradation of DNA induced in these cells by radiation exposure (500 cGy). Both the bFGF- and the TPA-mediated inhibition of apoptosis could be reversed by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (20 microM). These data demonstrate the involvement of PKC in the inhibition of radiation-induced apoptosis by bFGF and the rescue of endothelial cells from this mode of radiation-induced cell death.
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PMID:Protein kinase C mediates basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis. 816 85

PDGF heterodimer of A and B chains, a complete mitogen for 3T3 mouse fibroblasts, exemplifies those growth factors interacting with membrane associated tyrosine kinase receptors. Its binding to the PDGF-receptors results in receptor dimerization and subsequent activation of tyrosine kinase activity in the cytoplasmic protein domain, autophosphorylation of the receptor being the first event in the transduction cascade. Before the ligand-receptor complex is internalized and degraded, receptor stimulation is transmitted to the general transduction network, in which several tyrosine kinase substrates are activated by phosphorylation and changes the cytoplasmic biochemistry. These changes include cytoplasmic alkalinization, increases in the intracellular concentration of cyclic-AMP and Ca2+ and activation of protein kinase C through the degradation of phosphoinositides. The known substrates recruited by the PDGF-receptor association are phosphatidylinositol-3'-kinase, ras-GTPase-activating protein, phospholipase C-gamma, serine-threonine kinase Raf-1 and src and src-related tyrosine kinases. Upon binding of PDGF to its receptor, transactivation of transcriptional and nuclear factors such as c-fos and c-myc genes and dephosphorylation of c-jun occurs, V-sis, the oncogen of the simian sarcoma virus (SSV), is highly homologous to the c-sis/PDGF-B gene that encodes the homodimer of the B-chain of the PDGF receptor. Cells transformed by SSV have been studied as a model system for the autocrine stimulation of the PDGF receptor.
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PMID:Platelet derived growth factor/tyrosine kinase receptor mediated proliferation. 822 Jan 10

In the course of examining the actions of the cholecystokinin octapeptide (CCK-8) on pancreatic acini we found that CCK-8 can stimulate release of the large-molecular-weight cytoplasmic protein, lactate dehydrogenase (LDH) by as much as 6-fold. CCK-8-stimulated LDH release is mediated by a CCK-preferring receptor, detectable at 100 pM CCK-8, maximal at 100 nM CCK-8, constant for up to 30 min, reversible, not desensitized, and dependent on oxidative metabolism and incubation temperature but not on calcium in the extracellular medium. This action of CCK-8 is blocked by inhibitors of protein kinases, staurosporine, H-7, H-8 and H-9, but not by calmodulin antagonists, chlorpromazine, trifluoperazine or W-7. This action of CCK-8 on LDH release is not reproduced by TPA, 8Br-cAMP or A23187. Thus, it appears to be mediated by a previously uncharacterized protein kinase or an isoform of protein kinase C that is not maximally stimulated by TPA.
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PMID:A newly recognized action of cholecystokinin on pancreatic acini-release of lactate dehydrogenase. 849 90

Protooncogene c-fos is rapidly and transiently activated in response to a wide variety of stimuli and is therefore under a strict control of a great number of signal-transmitting systems. At the same time, the c-fos gene promoter has a complex organization since it determines the basic functional properties of this gene that are pertinent in cell differentiation and proliferation as well as in multiple stress responses. Interaction of external factors with the cell surface is accompanied by specific activation of intracellular processes promoting the interaction of definite transcription factors with the c-fos gene promoter. Depending on its mode, this interaction may trigger a wide range of signal-transmitting systems, in which membrane components (receptors, G- and Ras-proteins, adaptor proteins, tyrosine specific protein kinases) and cytoplasmic protein kinases (PKC, PKA, MAR-kinase cascade components) play a crucial role. Despite the linear mode of some of those pathways of signal transduction, many of their components interact with the concomitant factors which complicates signal transduction network but expands the potentialities of fine regulation of the c-fos gene.
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PMID:[Regulatory pathways of the c-fos proto-oncogene]. 860 Sep 89

The voltage-dependent L-type Ca2+ channel in the heart is regulated by cAMP-dependent protein kinase (PKA) and possibly by protein kinase C (PKC). We have investigated the channel modulation through phosphorylation by these protein kinases, using liposomes into which Ca2+ channels from bovine heart were reconstituted. Phosphorylation of the proteoliposomes with PKA increased the dihydropyridine-sensitive Ca2+ efflux from them by about 70%. PKA rapidly phosphorylated membrane proteins of 210 and 170 kDa. A dihydropyridine-class Ca2+ channel blocker, [3H]azidopine, specifically photo-labeled a protein of 210 kDa, suggesting that the 210-kDa phosphoprotein might be the alpha 1 subunit of the Ca2+ channel. In contrast, phosphorylation of the proteoliposomes with PKC failed to modulate the Ca2+ efflux. Although PKC catalyzed the phosphorylation of membrane proteins of 150, 130, 95, 67, and 62 kDa, the 210- and 170-kDa proteins were not phosphorylated by this kinase. These results suggest that phosphorylation of the 210-kDa protein in the cardiac sarcolemma by PKA may be responsible for modulation of the channel function, whereas modulation of the channel by PKC, if it occurs, must be the result of an indirect mechanism, e.g. phosphorylation of a cytoplasmic protein or an associated channel polypeptide, that cannot function in the reconstituted system.
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PMID:Cyclic AMP-dependent protein kinase but not protein kinase C regulates the cardiac Ca2+ channel through phosphorylation of its alpha 1 subunit. 886 60

We have previously reported that epidermal growth factor (EGF) augments the translation of pro-matrix metalloproteinase 3 (proMMP-3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs during the first 1-h treatment of human uterine cervical fibroblasts (Hosono, T. et al., FEBS Lett., 381, 115-118, (1996)). In this report, we have investigated the effect of interleukin 1 alpha (IL-1 alpha) and 12-O-tetradecanoylphorbol 13-acetate (TPA), potent stimulators of proMMPs and TIMP-1 production, on the translation of proMMP-3 and TIMP-1 mRNAs. When human uterine cervical fibroblasts were treated with IL-1 alpha or TPA for 2h, their translations were not augmented, whereas the steady-state levels of proMMP-3 and TIMP-1 mRNAs in the cells treated with these stimuli for 24 h were increased 13.3- and 1.3-fold by IL-1 alpha and 52.5- and 5.7-fold by TPA, respectively. By contrast, transforming growth factor alpha(TGF alpha), which also binds to EGF-receptor, enhanced their production as early as 2 h after treatment, indicating that growth factors that bind to EGF-receptor are likely to be involved in the translational enhancement of proMMP-3 and TIMP-1 mRNAs. EGF partially translocated cytoplasmic protein kinase C (PKC) to plasma membrane, but the PKC down-regulation induced by 100nM TPA did not diminish the EGF-mediated translational augmentation of proMMP-3 and TIMP-1 mRNAs. In contrast, the PKC inhibitor of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) effectively suppressed the translational regulation of proMMP-3 and TIMP-1 in a dose-dependent manner during the first 2-h treatment with EGF. These results suggest that EGF and TGF alpha, but not IL-1 alpha and TPA, specifically augment the translation of proMMP-3 and TIMP-1 mRNAs and accelerate their accumulation without modifying their transcripts during the first 1-2 h treatment of human uterine cervical fibroblasts. This translational augmentation is suggested to be mediated by a TPA-insensitive atypical PKC subclass in the PKC family.
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PMID:Translational augmentation of pro-matrix metalloproteinase 3 (prostromelysin 1) and a tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs by epidermal growth factor and transforming growth factor alpha, but not by interleukin 1 alpha or 12-O-tetradecanoylphorbol 13-acetate in human uterine cervical fibroblasts: the possible involvement of an atypical protein kinase C. 891 98


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