c-Src regulation of fibroblast growth factor-induced proliferation in murine embryonic fibroblasts.
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.
Kilkenny
Dawn M
DM
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Rocheleau
Jonathan V
JV
Price
James
J
Reich
Martha B
MB
Miller
Geraldine G
GG
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D016391:Genes, src / Q000502:physiology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D016220:Fibroblast Growth Factor 1