Abstract
Src family protein-tyrosine kinases have a central role in several biological functions, including cell adhesion and spreading, chemotaxis, cell cycle progression, differentiation and apoptosis. Surprisingly, these kinases also participate in mitogenic signalling by receptors that themselves exhibit an intrinsic protein-tyrosine kinase activity, inclu-ding those for platelet-derived growth factor (PDGF), epidermal growth factor and colony-stimulating factor-1. Indeed, Src kinases are strictly required for the nuclear expression 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 kinases participate in the induction of c-myc expression by tyrosine kinase receptors 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, thereby initiating the activation of a Rac-dependent pathway that controls the expression of the c-myc proto-oncogene.
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Acknowledgements
We thank H. Varmus, P. Schwartzberg, K. Aktories, R. Pestell, A. Aronheim and X. R. Bustelo for providing us with the pSM-Src YF and pSM-Src YFKM, CAIO-Src 251, pGEX2T-GST–CNF-1, pMyc-Luc, pRSV Sos myristoylated and Vav2 cDNAs, respectively; J. I. Lee for the gift of the anti-Vav2 antisera; and R. Visconti and S. Pece for many helpful discussions. M.C. was on leave from the Dipartimento di Biologia e Patologia Cellulare e Molecolare 'L. Califano', Università degli Studi di Napoli 'Federico II', via S. Pansini 5, 80131, Naples, Italy.
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Chiariello, M., Marinissen, M. & Gutkind, J. Regulation of c-myc expression by PDGF through Rho GTPases. Nat Cell Biol 3, 580–586 (2001). https://doi.org/10.1038/35078555
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DOI: https://doi.org/10.1038/35078555
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