Gastrin stimulates the formation of a p60Src/p125FAK complex upstream of the phosphatidylinositol 3-kinase signaling pathway

The molecular events whereby gastrin occupancy of G/CCKB receptors leads to phosphatidylinositol (PI) 3-kinase activation have been examined, We report here that this peptide promotes the association between two non-receptor tyrosine kinases, p60(Src) and p125(FAK), and elicits a parallel increase in tyrosine phosphorylation and activity of both kinases. Gastrin-induced PI 3-kinase activity was coprecipitated with p60(Src) and p125(FAK) and was inhibited by herbimycin A, the selective Src inhibitor PP-2 or cytochalasin D, which disrupts the actin cytoskeleton and prevents p125(FAK) activity. These results indicate, for the first time, that a p60(Src)/p125(FAK) complex acts upstream of the gastrin-stimulated PI 3-kinase pathway, (C) 1999 Federation of European Biochemical Societies.