Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory stimuli enhance the adherence properties of human umbilical vein endothelial cells (HUVEC) for neutrophils (PMN). This is mediated in part by the up-regulation on HUVEC of Intercellular Adhesion Molecule 1 (ICAM 1). Phorbol esters, which activate protein kinase c (PKC), have also been reported to enhance the adherence properties of HUVEC for PMN. We investigated the effect of agents which activate PKC on the expression of ICAM 1 by HUVEC. Both phorbol myristate acetate (PMA) and Mezerein, a non-phorbol which also stimulates PKC, enhanced both the expression of ICAM 1 on HUVEC and the adherence of HUVEC for PMN. The PKC inhibitors staurosporine and H-7 prevented both PMA and Mezerein-induced stimulation of HUVEC expression of ICAM 1 and adherence for PMN. We conclude that activation of PKC in HUVEC is associated with increased expression of ICAM 1 on HUVEC. PKC-mediated up-regulation of ICAM 1 may be responsible, in part, for the promotion of endothelial cell adherence properties toward PMN.
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PMID:Modulation of endothelial cell expression of intercellular adhesion molecule 1 by protein kinase C activation. 274 93

Activation of protein kinase C in erythrocytes by 4-beta-phorbol 12-myristate 13-acetate (PMA) resulted in a parallel stimulation (time course and dose response) of the phosphorylation of both membrane proteins (heterodimers of 107 kDa and 97 kDa, protein 4.1 and 4.9, respectively) and of phosphatidylinositol 4-phosphate (PIP) and, to a lesser extent, of phosphatidylinositol 4,5-bisphosphate (PIP2). Evidence that the effect on lipid was mediated by protein kinase C activation and not by a direct action of PMA was provided by (1) the lack of effect of a phorbol ester that did not activate protein kinase C or of PMA addition on isolated membranes from control erythrocytes, (2) the reversal of the effect in the presence of protein kinase C inhibitors (alpha-cobrotoxin, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine) or trifluoperazine). PMA treatment did not change the specific activity of ATP or the content of PIP2, but increased the content of PIP and decreased that of PI, indicating that the phosphorylation or dephosphorylation reactions linking PI and PIP were the target for the action of PMA. PMA treatment had no effect on the Ca2+-dependent PIP/PIP2 phospholipase C activity measured in isolated membranes. Mezerein, another protein kinase activator, had similar effects on both protein and lipid phosphorylation, when added with alpha-cobrotoxin. Activation of protein kinase A by cAMP also produced increases in phosphorylation, although quantitatively different from those induced by protein kinase C, in proteins and PIP. Simultaneous addition of PMA and cAMP at maximal doses resulted in only a partially additive effect on PIP labelling. These results show that inositol lipid turnover can be modulated by a protein kinase C and protein kinase A-dependent process involving the phosphorylation of a common protein. This could be PI kinase or PIP phosphatase or another protein regulating the activity of these enzymes.
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PMID:Stimulation of polyphosphoinositide turnover upon activation of protein kinases in human erythrocytes. 283 Sep 6

Mezerein, classified as a second-stage tumor promoter, has no diacylglycerol-like structure in its molecule, but can activate protein kinase C both in vitro and in vivo. This non-phorbol diterpene competitively inhibits the specific binding of a radioactive tumor-promoting phorbol ester to the enzyme. It is suggestive that tumor-promoting phorbol esters and mezerein cause analogous changes in the membrane to activate protein kinase C, and utilize this protein kinase as a common receptive protein for tumor promotion.
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PMID:Activation of protein kinase C by non-phorbol tumor promoter, mezerein. 623 78

The effects of protein kinase C (PKC) activators on gamma-aminoburyric acid (GABA) rho 1 receptor function were studied in rho 1 -expressing Xenopus oocytes. The PKC activator phorbol 12-myristate 13-acetate (PMA) but not the inactive analog phorbol 12-mono-myristate inhibited the GABA-gated chloride currents. Mezerein, a non-phorbol ester type PKC activator, also inhibited the rho 1 responses, but 8-chlorophenylthio-cyclic AMP, a protein kinase A activator, had no effect. The effect of PMA was significantly reduced by a PKC inhibitor, staurosporine. These results suggest that GABA rho 1 receptor function can be regulated by PKC-mediated phosphorylation events.
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PMID:GABA rho1 receptor: inhibition by protein kinase C activators. 871 30