Tyrosine phosphorylation of insulin receptor substrate-1 and activation of the PI-3-kinase pathway by glycine-extended gastrin precursors

Glycine-extended gastrin precursors (G-Gly) were considered as processing intermediates devoid of biological activity. However, we have recently identified selective receptors for G-Gly which mediate the proliferative effects of this precursor. Little is known about the signaling pathways activated by G-Gly. In the present study, we demonstrate that PI-3-kinase is rapidly and transiently activated by G-Gly. We also observed a rapid increase in the tyrosine phosphorylation of IRS-1 and an activation of the PI-3-kinase in anti-IRS-1 immunoprecipitates, suggesting that PI-3-kinase may be activated by association with tyrosine phosphorylated IRS-1, We also demonstrated that gastrin precursors activate the serine/threonine kinase, p70 kDa S6 kinase (p70(S6K)), through a wortmannin sensitive pathway. (C) 1997 Academic Press.