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)

The naphthalene sulfonamide calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, both induce limited myeloid differentiation of the human promyelocytic cell line, HL-60. In addition, these inhibitors augment the differentiation observed when HL-60 cells are induced with retinoic acid, dimethyl sulfoxide, or dibutyryl cyclic adenosine monophosphate. The dose-response curve for HL-60 differentiation was consistent with the published 50% inhibitory dose for inhibition of calmodulin-activated phosphodiesterase and with the calmodulin drug-binding potential of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide and their less active congeners, N-(6-aminohexyl)-1-naphthalenesulfonamide and N-(4-aminobutyl)-2-naphthalenesulfonamide. These effects, of the naphthalene sulfonamide calmodulin antagonists, are consistent with a regulatory role for calmodulin in cell differentiation, but parallel effects on protein kinase C cannot be excluded.
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PMID:Induction of myeloid differentiation of HL-60 cells with naphthalene sulfonamide calmodulin antagonists. 300 85

IL-1 and TNF-alpha are induced in macrophages by LPS; however, it is unclear whether similar mechanisms control the expression of both genes. Here, we report on the detection of differential regulation of LPS induced IL-1 and TNF-alpha mRNA expression and protein production in murine macrophages based on the use of inhibitors of second messenger pathways. Northern blot analysis was performed with total RNA obtained from murine (C57Bl/6) peritoneal macrophages stimulated in vitro with LPS with or without an inhibitor of protein kinase C (PKc)(1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride; H7) or an inhibitor of calmodulin (CaM)-dependent kinase (N-(6-amino-hexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride; W7). Northerns were analyzed with probes for IL-1 alpha and IL-1 beta and TNF-alpha. The expression of the three cytokine mRNA by LPS was inhibited in a dose response manner by H7. In contrast, the expression of IL-1 mRNA, but not TNF-alpha mRNA, was blocked by treatment with W7. Parallel studies monitoring biologic activities of these two cytokines confirm the mRNA data. PKc inhibitors, H7 and retinal, block both IL-1 and TNF-alpha protein production and inhibitors of CaM kinase, W7, N-(6-aminobutyl)-5-chloro-2-naphthalenesulfonamide, calmidazolum, and trifluoperazine dichloride inhibit only IL-1 production. These data suggest that both PKc and CaM kinase dependent pathways are involved in the induction of IL-1 mRNA by LPS. In contrast, TNF-alpha expression appears to be PKc dependent but not CaM kinase dependent.
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PMID:Differential inhibition of IL-1 and TNF-alpha mRNA expression by agents which block second messenger pathways in murine macrophages. 326 79

We have recently shown that calmodulin (CaM) regulates the trafficking of epidermal growth factor receptor (EGFR) as well as the mitogen-activated protein kinase (MAPK) signalling pathway. However, the overall regulation of the MAPK pathway is achieved through a complex interplay of other several upstream effectors including G-proteins, EGF, EGFR, protein kinase C (PKC), phosphatidylinositol-3-kinase and CaM. In order to understand the role of CaM in the PKC-mediated transactivation of EGFR we have analysed the effect of a CaM antagonist, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, on the 12-O-tetradecanoylphorbol-13-acetate-mediated activation of EGFR and the subsequent MAPK activation. The results show that CaM interferes with MAPK activation and the transactivation of EGFR mediated by PKC.
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PMID:Role of calmodulin in the modulation of the MAPK signalling pathway and the transactivation of epidermal growth factor receptor mediated by PKC. 1206 38