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)

We examined the expression of the proto-oncogene c-fos and the early growth response gene, Egr-1, in Rat 1 fibroblasts expressing high levels of normal or mutated human insulin receptors (McClain, D. A., Maegawa, H., Lee, J., Dull, T. J., Ullrich, A., and Olefsky, J. M. (1987) J. Biol. Chem. 262, 14663-14671). In cells expressing large numbers of normal human insulin receptors (HIRc-B cells), insulin (greater than or equal to 0.7 nM) stimulated the rapid accumulation of mRNAs for both genes. This response was blunted, but not lost, in cells expressing large numbers of human insulin receptors missing 43 amino acids at the carboxyl terminus of the beta-subunit. In contrast, the insulin response was completely absent in cells expressing large numbers of receptors that contained a mutation at the ATP-binding site that destroyed intrinsic protein tyrosine kinase activity (A/K 1018-B cells). This mutation also suppressed the modest transcriptional response to insulin that occurred in the parental Rat 1 cells. The transcriptional response to serum was normal in the A/K 1018-B cells, even after protein kinase C depletion; however, the response to insulin-like growth factor I was essentially lost. These studies suggest that overexpression of a kinase-deficient insulin receptor can suppress the transcriptional response to both insulin and insulin-like growth factor I that is ordinarily transduced through endogenous insulin and insulin-like growth factor I receptors, respectively. Competition for shared substrates of these related receptor kinases is a potential mechanism for this effect.
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PMID:Cellular expression of mutant insulin receptors interferes with the rapid transcriptional response to both insulin and insulin-like growth factor I. 198 10

In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested (Parker, P.J., Coussens, L., Totty, N., Rhee, L., Young, S., Chen, E., Stabel, S., Waterfield, M.D., and Ullrich, A. (1986) Science 233, 853-859). In the present report, we demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes, and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn2+, while Fe2+ and Mn2+ are only partially counteractive. Our results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca2+, phorbol ester, or antigen.
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PMID:Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes. 325 66

Release of large soluble NH2-terminal fragments of the amyloid precursor protein (APP) of Alzheimer's disease was measured in two Swiss 3T3 fibroblast cell lines (designated SF1.4 and SF3.2), overexpressing the alpha subtype of protein kinase C, and in two control cell lines (SC1 and SC2) (Eldar, H., Zisman, Y., Ullrich, A., and Livneh, E. (1990) J. Biol. Chem. 265, 13290-13296). Basal release of APP was significantly increased in SF1.4 cells, but not in SF3.2 cells, relative to controls. Phorbol 12-myristate 13-acetate, an activator of protein kinase C, elicited a concentration-dependent increase in APP release in all four cell lines. However, the estimated EC50 for this effect was lower in the two cell lines overexpressing protein kinase C-alpha (7 and 6 nM, in SF1.4 and SF3.2 cells, respectively) than in control SC1 and SC2 cells (56 and 22 nM, respectively). The absolute amount of APP released by maximal concentrations of phorbol ester was not altered by overexpression of protein kinase C alpha. The protein kinase C inhibitor H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) significantly reduced the response to phorbol esters in control (SC1) cells but not in cells (SF1.4) that overexpress protein kinase C alpha. Levels of cell-associated APP were slightly elevated, and rates of APP turnover were unchanged, in SF1.4 cells relative to controls. However, cell-associated APP levels were lower in SF3.2 cells than in controls. The results demonstrate that protein kinase C alpha regulates APP release in Swiss 3T3 fibroblasts, and perhaps in other tissues, including brain, and may be the isozyme that mediates receptor-evoked release of APP.
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PMID:Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase C alpha. 840 46