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 (p70S6K), through a wortmannin sensitive pathway.
Kowalski-Chauvel
A
A
INSERM U.151, Groupe de Recherche de Biologie et Pathologie digestive, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
Pradayrol
L
L
Vaysse
N
N
Seva
C
C
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007700:Kinetics; D010190:Pancreatic Neoplasms; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005755:Gastrins; D005998:Glycine; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019000:Phosphotyrosine; D011498:Protein Precursors; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin; C526296:Irs1 protein, rat