Activation of Src family members is not required for the platelet-derived growth factor beta receptor to initiate mitogenesis.

Molecular and Cellular Biology
K A DeMali, A Kazlauskas

Abstract

The basal activity of Src family kinases is readily detectable throughout the cell cycle and increases by two- to fivefold upon acute stimulation of cells with growth factors such as platelet-derived growth factor. Previous reports have demonstrated a requirement for Src activity for the G1/S and G2/M transitions. With a chimeric alpha-beta PDGF receptor (PDGFR) expressed in fibroblasts, we have investigated the importance of the PDGF-mediated increase in Src activity at the G0/G1 transition for subsequent cell cycle events. A mutant PDGFR chimera that was not able to detectably associate with or activate Src was compromised in its ability to mediate tyrosine phosphorylation of receptor-associated signaling molecules and initiated a submaximal activation of Erk. In contrast to these early cell cycle events, later responses such as entry of cells into S phase and cell proliferation proceeded normally when Src activity did not increase following acute stimulation with PDGF. We conclude that the initial burst of Src activity is required for efficient tyrosine phosphorylation of receptor-associated proteins such as PLCgamma, RasGAP, Shc, and SHP-2 and for maximal activation of Erk. Surprisingly, these events are not required for PD...Continue Reading

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Citations

Aug 27, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A OliveraS Spiegel
Mar 3, 2004·Molecular and Cellular Biology·Rina PlattnerAnn Marie Pendergast
Aug 9, 2007·The Journal of Biological Chemistry·Eunok Im, Andrius Kazlauskas
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Mar 15, 2006·Cellular Signalling·Goutam Ghosh ChoudhuryNandini Ghosh-Choudhury
Dec 26, 2001·Chemical Reviews·S M Jones, A Kazlauskas

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