Regulation of c-myc expression by PDGF through Rho GTPases

Src family protein-tyrosine kinases have a central role in several biologic al functions, including cell adhesion and spreading, chemotaxis, cell cycle progression, differentiation and apoptosis. surprisingly, these kinases al so participate in mitogenic signalling by receptors that themselves exhibit an intrinsic protein-tyrosine kinase activity, including those for platele t-derived growth factor (PDGF), epidermal growth factor and colony-stimulat ing factor-1. Indeed, Src kinases are strictly required for the nuclear exp ression of the c-myc proto-oncogene and thus for DNA synthesis in response to PDGF. However, the nature of the signalling pathways by which Src kinase s participate in the induction of c-myc expression by tyrosine kinase recep tors is still unknown. Here we show that PDGF enhances c-myc expression and stimulates the c-myc promoter in a Src-dependent manner, and that neither Ras nor the mitogen-activated protein kinase pathway mediate these effects. In contrast, we present evidence that PDGF stimulates Vav2 through Src, th ereby initiating the activation of a Rac-dependent pathway that controls th e expression of the c-myc proto-oncogene.