Differential inhibition of the epidermal growth factor-, platelet-derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251

摘要: The microbial alkaloid staurosporine is a potent but nonselective inhibitor of protein kinases. derivative CGP 41251 has been shown to exert high degree selectivity for inhibition kinase C activity. Both compounds are powerful inhibitors proliferation both normal and transformed cells in vitro antitumor efficacy vivo. In this work we have studied the mode action these by analyzing their effects on early events induction different growth stimuli. drugs blocked phorbol ester-induced expression c-fos proto-oncogene. effect was reversible, since its removal led mRNA response 12-myristate 13-acetate. Submicromolar concentrations directly inhibited platelet-derived factor (PDGF) receptor autophosphorylation induced PDGF stimulation intact BALB/c 3T3 cells. contrast, ligand-induced epidermal autokinase activity A431 carcinoma factor-dependent were relatively insensitive 41251. Staurosporine suppressed signal generation reducing overall levels receptor. We conclude that reversible PDGF-mediated transduction. It inhibits tyrosine subsequent signaling cascade. broad kinases also reflected at cellular level might contribute toxicity compound, comparison