c-Src regulation of fibroblast growth factor-induced proliferation in murine embryonic fibroblasts

J Biol Chem. 2003 May 9;278(19):17448-54. doi: 10.1074/jbc.M209698200. Epub 2003 Mar 5.

Abstract

Activated fibroblast growth factor receptor 1 (FGFR1) propagates FGF signals through multiple intracellular pathways via intermediates FRS2, PLCgamma, and Ras. Conflicting reports exist concerning the interaction between FGFR1 and Src family kinases. To address the role of c-Src in FGFR1 signaling, we compared proliferative responses of murine embryonic fibroblasts (MEF) deficient in c-Src, Yes, and Fyn to MEF expressing either endogenous levels or overexpressing c-Src. MEF with endogenous c-Src had significantly greater FGF-induced DNA synthesis and proliferation than cells lacking or overexpressing c-Src. This was related directly to c-Src expression by analysis of c-Src-deficient cells transfected with and sorted for varying levels of a c-Src expression vector. This suggests an "optimal" quantity of c-Src expression for FGF-induced proliferation. To determine if this was a general phenomenon for growth factor signaling pathways utilizing c-Src, responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and lysophosphatidic acid (LPA) were examined. As for FGF, responses to EGF were clearly inhibited when c-Src was absent or overexpressed. In contrast, varying levels of c-Src had little effect on responses to PDGF or LPA. The data show that mitogenic pathways activated by FGF-1 and EGF are regulated by c-Src protein levels and appear to differ significantly from those activated by PDGF and LPA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line
  • Fibroblast Growth Factor 1 / pharmacology*
  • Fibroblasts / cytology*
  • Fibroblasts / physiology
  • Gene Expression Regulation / drug effects
  • Genes, src / physiology*
  • Mice
  • Platelet-Derived Growth Factor / pharmacology

Substances

  • Platelet-Derived Growth Factor
  • Fibroblast Growth Factor 1