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

Abstract
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, p60Src and p125FAK, and elicits a parallel increase in tyrosine phosphorylation and activity of both kinases. Gastrin‐induced PI 3‐kinase activity was coprecipitated with p60Src and p125FAK and was inhibited by herbimycin A, the selective Src inhibitor PP‐2 or cytochalasin D, which disrupts the actin cytoskeleton and prevents p125FAK activity. These results indicate, for the first time, that a p60Src/p125FAK complex acts upstream of the gastrin‐stimulated PI 3‐kinase pathway.