Murine cortactin is phosphorylated in response to fibroblast growth factor-1 on tyrosine residues late in the G1 phase of the BALB/c 3T3 cell cycle.

We have previously reported that BALB/c 3T3 cells require a prolonged exposure to fibroblast growth factor (FGF)-1 for the stimulation of maximal DNA synthesis, and this event correlates with the tyrosine phosphorylation of novel proteins late in G1 including a protein termed p80/p85 (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 9611-9620). We have purified, sequenced, and cloned the cDNA encoding p80/p85 and report that it is the murine homolog of the chicken cortactin gene and a member of the human hematopoietic specific-1 gene family. Immunochemical analysis of m-cortactin-tyrosine phosphorylation in response to FGF-1 demonstrates a biphasic phosphorylation pattern both as a weak immediate-early and strong mid to late G1 response protein. Because the chicken cortactin gene was originally isolated as a substrate for v-Src, FGF-1 may influence the enzymatic activity of other cell-associated tyrosine kinases which utilize p80/p85 (cortactin) as a polypeptide substrate.