Src is required for cell migration and shape changes induced by fibroblast growth factor 1

Oncogene. 1999 Nov 18;18(48):6700-6. doi: 10.1038/sj.onc.1203050.

Abstract

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.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Membrane / physiology*
  • Cell Size / physiology*
  • Fibroblast Growth Factor 1
  • Fibroblast Growth Factor 2 / physiology*
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / physiology*
  • Tyrosine / metabolism

Substances

  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Tyrosine
  • Proto-Oncogene Proteins pp60(c-src)