Involvement of tyrosine kinase and protein kinase C in platelet-activating-factor-induced c-fos gene expression in A-431 cells.

摘要: In A-431 cells, platelet-activating factor (PAF) induces the expression of c-fos and TIS-1 genes in both absence presence cycloheximide a structurally specific receptor-coupled manner. We have now investigated molecular mechanisms this response, particularly relation to role protein kinases. Pretreatment cells with genistein or methyl-2,5-dihydroxycinnamate (tyrosine kinase inhibitors) staurosporine (a C inhibitor) for 20 min abolished induced by PAF. Interestingly, when was added 90 s after addition PAF, no inhibition observed. Similarly, did not inhibit 8 PAF cells. These inhibitions were dose-dependent (IC50 180 nM, 50 microM). Simultaneous phorbol 12-myristate 13-acetate (PMA) give synergistic effect on expression. PMA had [3H]PAF binding, but PAF-induced gene PAF-stimulated desensitized if pretreated epidermal growth able stimulate PAF-desensitized thus indicated involvement distinct two stimuli. Forskolin, an activator adenylate cyclase, induce response. Exposure as little 1 min, followed its removal, sufficient activate demonstrated rapidity exquisite nature signalling involved process. It is concluded that activation receptor proposed G-protein-coupled receptor) causes rapid production signals which mediated via tyrosine C.