Tyrosine phosphorylation of insulin receptor substrate-1 and activation of the PI-3-kinase pathway by glycine-extended gastrin precursors
Kowalski-Chauvel, A.; Pradayrol, L.; Vaysse, N.; Seva, C.
Biochemical and Biophysical Research Communications 236(3): 687-692
1997
ISSN/ISBN: 0006-291X PMID: 9245714 DOI: 10.1006/bbrc.1997.6975
Accession: 047861160
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.