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 .

Susa M ; Vulevic D ; Lane HA ; Thomas G

Friedrich Miescher Institute , Basel , Switzerland .

J Biol Chem 267 : 6905-9 ( 1992)

Abstract
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 -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 .