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)

The changes in protein phosphorylation associated with bovine tracheal smooth muscle contraction were studied by labeling intact muscle strips with [32P]PO4(3-) and analyzing the phosphoproteins by two-dimensional gel electrophoresis. Among 20 to 30 phosphoproteins resolvable with the two-dimensional electrophoresis system, the phosphorylation of 12 proteins was reproducibly affected by treatment with carbachol, in a time-dependent manner. Five of these proteins have been identified as 20-kDa myosin light chain, caldesmon, synemin, and two isoelectric variants of desmin. The other 7 are low molecular weight (Mr less than 40,000) cytosolic proteins. One cytosolic protein and myosin light chain are quickly but transiently phosphorylated by carbachol, the peak of myosin light chain phosphorylation being at about 1 min after agonist addition. In contrast, both variants of desmin, synemin, caldesmon, and 5 cytosolic proteins are phosphorylated at varying rates and remain phosphorylated for the duration of carbachol action. These "late" phosphorylation changes occur simultaneously with the dephosphorylation of one cytosolic protein. These carbachol-induced phosphorylation changes, like the contractile response, appear to be calcium-dependent. The addition of 12-deoxyphorbol 13-isobutyrate, a protein kinase C activator, causes a dose-dependent, sustained contraction of tracheal smooth muscle which develops more slowly than that induced by carbachol. This contractile response is associated with the same protein phosphorylation changes as those observed after prolonged carbachol treatment. In contrast, forskolin, an adenylate cyclase activator and a potent smooth muscle relaxant, induces the phosphorylation protein 3 and one variant of desmin. These observations strongly suggest that different phosphoproteins may be mediators of tension development and tension maintenance in agonist-induced contraction of tracheal smooth muscle.
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PMID:Carbachol-induced protein phosphorylation changes in bovine tracheal smooth muscle. 378 86

The pattern of protein phosphorylation induced by phorbol-12-myristate-13-acetate (PMA) was analyzed by two-dimensional gel electrophoresis in human HL-60 leukemia cells, which are susceptible to induction of cell differentiation by PMA, and in cells from an HL-60 cell variant designated R-94 that are resistant to such an induction. Protein phosphorylation was detected by observing either a rapid acid-directed charge shift of [35S]methionine-labeled protein or an increase in the amount of phosphate label in a 32P-labeled protein. The results indicated that PMA at 10(-7) M causes within 30 min after treatment the phosphorylation of at least ten different proteins in both the HL-60 and R-94 cells. Among these ten phosphorylated proteins, we identified a major cytoplasmic polypeptide (Mr approximately 64,000), a cytoskeletal protein (Mr approximately 56,000), a nonmuscle myosin light chain, and two proteins (Mr approximately 60,000 and 64,000) localized in or around the cell nucleus. Phosphoamino acid analysis of six of the ten phosphoproteins showed that they contain phosphoserine. None of these proteins contained phosphotyrosine or phosphothreonine. The R-94 cell variant was found to be capable of increased protein phosphorylation after PMA treatment; however, the level of phosphate incorporation reached only the level of the untreated HL-60 cells and thus fell far short of the level observed in the HL-60 cells after PMA treatment. It is suggested that the basis for the acquired resistance in R-94 cells towards induction of cell differentiation by PMA is a block in signal transmission involving phosphorylation of nuclear protein(s) following the binding of the inducer PMA to its receptor (protein kinase C).
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PMID:Specific protein phosphorylation in human promyelocytic HL-60 leukemia cells susceptible or resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate. 386 Dec 40

In human platelets, the Ca2+ ionophore A23187 stimulated the phosphorylation of a 40 kDa protein and myosin light chain (MLC) to the same extents as those induced by thrombin, but the doses of A23187 for 40 kDa protein phosphorylation were higher than those for MLC phosphorylation, although the doses of thrombin for both reactions were nearly the same. Moreover, A23187 produced much less diacylglycerol than thrombin. However, the sites of the 40 kDa protein phosphorylated by the action of A23187 and thrombin were identical, and the 40 kDa protein phosphorylation induced by A23187 and thrombin was inhibited by tetracaine, an inhibitor for protein kinase C. Neither A23187 nor thrombin induced the production of a catalytic fragment of protein kinase C which might be generated by limited proteolysis with Ca2+-dependent protease. These results indicate that A23187 induces protein kinase C activation which phosphorylates the 40 kDa protein, but higher doses of A23187 are required for the activation of this enzyme than for the activation of MLC kinase.
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PMID:Comparison of the modes of action of Ca2+ ionophore A23187 and thrombin in protein kinase C activation in human platelets. 393 95

Platelet secretion in response to physiologic stimuli appears to result from the complementary stimulation of two processes--granule centralization and granule membrane fusion. Granule centralization is produced by actin-myosin contraction which is initiated by a movement of calcium ions into the cytoplasm. The calcium binds to calmodulin to form a complex which activates myosin light chain kinase to phosphorylate myosin light chain (MLC). Once phosphorylated in this fashion, actin-myosin contraction occurs. Granule membrane fusion can be produced selectively by phorbol myristate acetate and oleoyl-acetyl diglyceride, both of which activate protein kinase C. Phosphorylation of a 47,000 dalton intracellular protein (47K) by protein kinase C may be critical to granule membrane fusion. The mechanism of action of 47K is presently unknown. The combined phosphorylation of MLC and 47K in response to most physiologic agonists which cause granule secretion, and the synergistic effects on granule secretion of agents which independently stimulate MLC and 47K phosphorylation, suggests secretion usually results from the interaction of granule centralization and granule membrane fusion.
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PMID:Protein phosphorylation and platelet secretion. 405 47

The activation of protein kinase C in human platelets by phorbol-12, 13- dibutyrate (PDBu) results in the phosphorylation of a 40,000 dalton protein. This phosphorylation is time- and concentration-dependent. Maximal phosphorylation is rapid and is not affected by indomethacin or prostacyclin. PDBu does not promote activation of the phosphodiesteratic cleavage (phospholipase C) of the inositol phospholipids and the subsequent formation of 1,2-diacylglycerol or its phosphorylated product, phosphatidic acid. If platelets exposed to PDBu are subsequently stimulated with thrombin, this stimulus does not initiate further 40,000 dalton protein phosphorylation but will promote the formation of phosphatidic acid and also the phosphorylation of a 20,000 dalton protein (myosin light chain). However, prostacyclin will prevent the subsequent stimulation of phosphatidic acid synthesis by thrombin in a concentration-dependent manner. The fact that prostacyclin can affect the response to thrombin, even in the presence of phorbol ester, supports the idea that the enzymes related to the formation of phosphatidic acid or inhibition of its synthesis are not related to the phosphorylated 40K protein.
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PMID:Prostacyclin inhibition of phosphatidic acid synthesis in human platelets is not mediated by protein kinase C. 623 30

In human platelets, serotonin is known to induce a shape change followed by (reversible) aggregation. Recently, it was found that the amine triggers the elevation of cytosolic free calcium and activates phospholipase C. On stimulation of human platelets with serotonin we found an immediate increase in protein kinase C activity, phosphorylating its 40 kDa substrate protein. A 20 kDa protein, most likely the myosin light chain, was phosphorylated to the same extent. Ketanserin, a highly selective serotonin-S2 antagonist inhibited both phosphorylation processes at subnanomolar concentrations.
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PMID:Stimulation by serotonin of 40 kDa and 20 kDa protein phosphorylation in human platelets. 623 73

Cd2+ was found to mimic effectively, potentiate and antagonize the stimulatory action of Ca2+ on myosin light chain kinase (MLCK) and phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca-PK, or protein kinase C). PL-Ca-PK, however, was slightly less sensitive to Cd2+ regulation than was MLCK. Cd2+ also biphasically regulates (i.e., stimulation followed by inhibition) phosphorylation, in the homogenates of the rat caudal artery, of myosin light chain and other endogenous proteins catalyzed by MLCK and PL-Ca-PK. The activation by Cd2+ of MLCK was inhibited by anticalmodulins (e.g., R-24571), whereas the inhibition by a higher Cd2+ concentration of MLCK and PL-Ca-PK was reversed by thiol agents (e.g., cysteine). The present findings may provide one mechanism underlying the vascular toxicity of Cd2+, a major environmental pollutant.
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PMID:Environmental pollutant Cd2+ biphasically and differentially regulates myosin light chain kinase and phospholipid/Ca2+-dependent protein kinase. 623 26

1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7), which has been identified as a potent inhibitor of protein kinase C in vitro (Hidaka, H., Inagaki, M., Kawamoto, S., and Sasaki, Y. (1984) Biochemistry, in press), enhanced serotonin release from human platelets that was induced by the 12-O-tetradecanoyl phorbol 13-acetate and correspondingly decreased incorporation of radioactive phosphate into a 20,000-dalton protein. H-7 did not affect the protein phosphorylation or the serotonin secretion in unstimulated platelets. A phosphopeptide with a molecular weight of 20,000 has previously been identified as a light chain (LC20) of platelet myosin and both protein kinase C and Ca2+-calmodulin-dependent myosin light-chain kinase have been shown to be involved in its phosphorylation. Two-dimensional peptide mapping following tryptic hydrolysis revealed that H-7 selectively inhibited the protein kinase C-catalyzed phosphorylation of myosin light chain. This pharmacological evidence suggests that Ca2+-activated, phospholipid-dependent myosin light-chain phosphorylation may play an inhibitory role in the release reaction.
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PMID:Serotonin secretion from human platelets may be modified by Ca2+-activated, phospholipid-dependent myosin phosphorylation. 623 60

Degradation of inositides induced by phospholipase C in activated platelets leads to the formation of 1,2-diacylglycerol (1,2-DG) and its phosphorylated product, phosphatidic acid (PA). We have studied the relationship between activation of phospholipase C and the appearance of specific platelet responses, such as phosphorylation of proteins, shape change, release reaction and aggregation induced by different stimuli such as thrombin, platelet-activating factor, collagen, arachidonic acid (AA) and dihomogamma linolenic acid. A low degree of platelet activation induces only shape change which is associated with partial activation of phospholipase C (formation of phosphatidic acid), and phosphorylation of both a 40K molecular weight protein (protein kinase C activation) and a 20K molecular weight protein (myosin light chain). A higher degree of platelet activation induces aggregation, release of serotonin and a higher level of phospholipase C and protein kinase C activities. Metabolism of AA occurs concomitantly to aggregation and serotonin release, but AA metabolites are not related to the shape change of human platelets. Platelet shape change and the initial activation of phospholipase C induced by thrombin or platelet-activating factor is independent of the metabolites derived from cyclo-oxygenase activity. Further activation of phospholipase C which occurs during platelet aggregation and release reaction is, however, partly dependent on cyclo-oxygenase metabolites.
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PMID:The role of phospholipase C in platelet responses. 641 9

Phosphorylation of the 20,000 molecular weight (MW) light chain of platelet myosin is associated with the activation of platelets and subsequent release of platelet granules, and the protein kinase catalysing this phosphorylation has been identified as the Ca2+/calmodulin-dependent enzyme, myosin light chain kinase. Tumour-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA), which activate Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), can also cause platelet aggregation and phosphorylation of a 20,000-MW peptide in blood platelets. It was therefore of interest to ascertain whether the 20,000-MW peptide phosphorylated in platelets was the light chain of myosin and whether TPA-induced phosphorylation of the 20,000-MW peptide could be differentiated from thrombin-induced phosphorylation. We now report that TPA-induced activation of platelets is associated with the phosphorylation of the 20,000-MW light chain of myosin, that it appears to be mediated mainly through protein kinase C and that the site phosphorylated in the myosin light chain is distinct from that phosphorylated by myosin light chain kinase.
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PMID:Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains. 668 54


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