Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin.
The initiation of maximal DNA synthesis by fibroblast growth factor (FGF)-1 requires the presence of the growth factor during the entire G0 to G1 transition period of the cell cycle (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 9611-9620). During this time, the phosphorylation of several novel proteins on tyrosine residues occurs, and one of these phosphotyrosyl-containing proteins has been characterized as the murine homolog of the chicken cortactin gene (Zhan, X., Hu, X., Hampton, B., Burgess, W.H., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 24427-24431), a putative substrate for v-Src. We have examined the possibility that FGF-1 employs c-Src or Src-like kinases as signaling intermediates during the mid and late G1 phase of the NIH 3T3 cell cycle using immunoprecipitation and immunoblot analysis. We have demonstrated that c-Src can associate with cortactin in a FGF-1-dependent manner. We have also demonstrated that a monoclonal antibody prepared against FGF receptor (R)-1 is able to co-precipitate Src-related proteins in lysates from FGF-1-treated NIH 3T3 cells. Furthermore, a kinase-active form of FGFR-1 expressed in a bacterial system was also able to associate with Src kinases in a manner dependent on the phosphorylation status of the FGFR-1 protein. Lastly, the Src homology (SH)-2 domain of v-Src was able to recognize a recombinant form of FGFR-1. Because (i) the association between FGFR-1 and Src-like kinases exhibits kinetics similar to those observed between the Src kinases and cortactin and (ii) the Src-SH2 domain is likely to be involved in the association with FGFR-1, we propose that the association of c-Src with activated FGF receptors may be responsible for the tyrosine phosphorylation of cortactin during the mid to late G1 phase of the cell cycle.
Zhan
X
X
Department of Research, Hoffman Heart Institute, Saint Francis Hospital and Medical Center, Hartford, Connecticut 16501-1299.
Plourde
C
C
Hu
X
X
Friesel
R
R
Maciag
T
T
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D051356:Cortactin; D017931:DNA Primers; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D051356:Cortactin; C495869:Cttn protein, mouse; D017931:DNA Primers; D008840:Microfilament Proteins; D017468:Receptors, Fibroblast Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src)