MEMBRANE-PROTEIN KINASE-C ACTIVITY RAPIDLY INCREASES IN QUIESCENT TSRSV-INFECTED NRK CELLS UPON REACTIVATION OF THE MITOGENIC V-SRC PROTEIN-KINASE

The viral src protein kinase, pp60(v-src), is a powerful intracellular mitogen which can initiate and maintain the proliferation fo quiescent cells in the absence of any exogenous growth factors. In an attempt to understand how pp60(v-src) induces proliferation, we examined the early events in the G0 to G1 transition caused by the activation of a thermolabile v-src protein in quiescent, serum-starved tsRSV-transformed NRK cells. The reactivation of pp60(v-src), in the absence of exogenous growth factors, triggered a rapid biphasic surge of membrane-associated protein kinase C (PKC) activity. Unlike TPA-stimulated PKC activity, the pp60(v-src)-induced increase in PKC was readily extracted from membranes by EGTA. The down-regulation of PKC activity in these quiescent cells by prolonged exposure to TPA strongly inhibited the ability of the reactivated v-SRC protein to stimulate DNA replication in serum-deficient medium, suggesting that PKC plays a role in the initial signal by which the viral enzyme induced the G0 to G1 transition in NRK cells.