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, pp60v-src, is a powerful intracellular mitogen which can initiate and maintain the proliferation of quiescent cells in the absence of any exogenous growth factors. In an attempt to understand how pp60v-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 pp60v-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 pp60v-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 induces the G0 to G1 transition in NRK cells.
Durkin
J P
JP
Institute of Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Chakravarthy
B
B
Tremblay
R
R
Whitfield
J F
JF
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004789:Enzyme Activation / Q000502:physiology; D008934:Mitogens / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D008934:Mitogens; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D011493:Protein Kinase C