Src is required for cell migration and shape changes induced by fibroblast growth factor 1.
Fibroblast growth factor 1 (FGF-1) is a potent chemotactic factor and induces tyrosine phosphorylation of a cortical actin-associated protein (cortactin). The tyrosine phosphorylation of cortactin induced by FGF-1 requires the tyrosine residues 421, 482 and 466, which are targeted by the protein tyrosine kinase Src in vitro. Furthermore, FGF-1 is unable to induce tyrosine phosphorylation of cortactin within the cells derived from Src knockout mice (Src-/-), indicating that Src is required for the tyrosine phosphorylation of cortactin induced by FGF-1. Although Src-/- cells are able to undergo rapid proliferation, they are impaired to respond to FGF-1 for the shape change and cell migration. Morphological analysis further reveals that FGF-1 fails to induce the formation of polarized lamellipodia and the translocation of cortactin into the leading edge of Src-/- cells. Consistent with the mitogenic response to FGF-1, the lack of Src does not affect the tyrosine phosphorylation of Snt (or Frs2), a FGF-1 early signaling protein that links to Ras. Therefore, our data support the notion that Src and cortactin participate in a FGF signal pathway for cell migration and shape change rather than mitogenesis.
Liu
J
J
Department of Experimental Pathology, Holland Laboratory of American Red Cross, Rockville, MD 20855, USA.
Huang
C
C
Zhan
X
X
D016475:3T3 Cells; D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D048429:Cell Size / Q000502:physiology*; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)