Inhibition or down-regulation of protein kinase C attenuates late phase p70s6k activation induced by epidermal growth factor but not by platelet-derived growth factor or insulin.
The late phase of the time-dependent epidermal growth factor (EGF)-induced biphasic activation of the p70s6k is selectively attenuated by the specific PKC inhibitor, CGP 41,251, a staurosporine derivative. At a 40-fold lower concentration than CGP 41,251, staurosporine inhibits both phases of S6 kinase activation to the same extent, whereas the inactive staurosporine derivative CGP 42,700 shows no effect on either phase. Platelet-derived growth factor (PDGF) and insulin also induce biphasic S6 kinase activation, but in neither case is either phase of activation affected by the presence of CGP 41,251. This finding was unexpected in the case of PDGF, which is a potent activator of PKC and whose receptor directly interacts with phospholipase C gamma 1. However, similar results were obtained following down-regulation of PKC by prolonged 12-O-tetradecanoylphorbol-13-acetate treatment. Therefore, even though EGF and PDGF induce PKC activation, PDGF, unlike EGF, does not appear to use this signaling pathway for late phase p70s6k activation.
Susa
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M
Friedrich Miescher Institute, Basel, Switzerland.
Vulević
D
D
Lane
H A
HA
Thomas
G
G
D016475:3T3 Cells; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction; D019311:Staurosporine / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007328:Insulin; D010982:Platelet-Derived Growth Factor; C073761:CGP 42700; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin; D013755:Tetradecanoylphorbol Acetate