Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phorbol-12-myristate-13-acetate (PMA) inhibited growth of human mammary carcinoma cell lines and increased mainly the phosphorylation of two cytosolic phosphoproteins (pp) of 27 kD with isoelectric points of 5.5 (pp27a) and 5.0 (pp27b). The time course of pp27 phosphorylation closely paralleled the rapid PMA-induced subcellular redistribution of protein kinase C (PKC) activity and its subsequent down regulation. Addition of phospholipase C and fetal calf serum to intact cells or purified PKC to a cell free system enhanced the phosphorylation of both pp27 suggesting that the two polypeptides are specific substrates for PKC. Exposure of human mammary carcinoma cells to stress inducers such as arsenite or cadmium increased the 32P incorporation of both pp27 to an extent comparable to PMA. The increased phosphorus content following stress was rather due to a higher rate of synthesis of both pp27 than to a higher phosphorylation state of these polypeptides as determined by [3H]-leucine labeling. These results indicate that the major substrates of PKC, phosphorylated during the PMA-induced growth inhibition of human mammary carcinoma cells, are members of the stress protein family, suggesting a new possible function for these proteins.
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PMID:The 27,000 daltons stress proteins are phosphorylated by protein kinase C during the tumor promoter-mediated growth inhibition of human mammary carcinoma cells. 335 73

The importance of alpha-thrombin in the clotting cascade is well-known, but it is also a potent mitogen. Like many other mitogens, thrombin causes receptor-mediated activation of a phosphatidylinositol-specific phospholipase C (PLC), leading to the release of diacylglycerol and the subsequent activation of protein kinase C (refs 3-6). Protein kinase C is probably important in cell proliferation, as activation of this enzyme by phorbol esters promotes growth in many systems. Some growth factors have tyrosine kinase activity and function without activation of PLC or protein kinase C. In this report we show that alpha-thrombin retains its mitogenicity in vascular smooth muscle cells depleted of protein kinase C. Phorbol-12-myristate-13-acetate (PMA) is found to be a potent growth inhibitor when added to vascular smooth muscle cells with alpha-thrombin. Moreover, growth inhibition is maximal when protein kinase C is activated 4 hours after exposure to thrombin, long after the completion of 'early events' induced by thrombin. Thus, PMA probes an event late in the G1 phase of the cell cycle or at the G1-S transition.
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PMID:Growth inhibition by protein kinase C late in mitogenesis. 367 Mar 89

The interaction of tumour promoters with the target cell type (keratinocyte) may be an essential feature of their promoting activity and their ability to initiate an inflammatory response. The role of prostaglandin E(2) (PGE(2)), particularly in the keratinocyte, remains largely unknown, but it is closely associated with inflammation and regenerative epidermal hyperplasia, which appear critical for tumour promotion. Rat keratinocytes derived from sublingual mucosa represent a suitable model to investigate the ability of several irritants, of varying tumour-promoting potency, to stimulate PGE(2) release. Cytotoxicity was evaluated by the neutral red uptake assay and a concentration that reduced cell viability to 50% of control was selected as a maximum concentration for subsequent measurement of PGE(2) release. Phorbol-12-myristate-13-acetate, ionophore A23187 and mezerein stimulated PGE(2) release at non-toxic concentrations. Anthralin, benzoyl peroxide, sodium dodecyl sulfate and acetic acid did not stimulate PGE(2) at non-toxic concentrations, but release was associated with a toxic response. Epidermal growth factor and phospholipase C, which are closely associated with intracellular signalling systems that modulate keratinocyte proliferation and differentiation, also stimulated PGE(2) release. Epidermal growth factor elicited PGE(2) release at a concentration reported to be mitogenic in keratinocyte cultures. The stimulation of PGE(2) release in the absence of a toxic response by PMA, mezerein and ionophore A23187 may be indicative of a direct interaction of the chemicals with intracellular pathways involved in regulation of keratinocyte differentiation and proliferation. This interaction may also reflect the ability of such chemicals to initiate an inflammatory response. Measurement of PGE(2) release may be useful to investigate further the mechanism of action of tumour promoters in the target cell type. In contrast, other tumour promoters did not stimulate release at non-toxic concentrations, which implies that their ability to initiate an inflammatory response and possibly their promoting activity is associated with the induction of a toxic response in the target cell population.
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PMID:Prostaglandin E(2) release in keratinocyte cultures following exposure to various tumour promoters. 2065 80