Gastrointestinal growth factors and hormones have divergent effects on Akt activation

摘要: Akt is a central regulator of apoptosis, cell growth and survival. Growth factors some G-protein-coupled receptors (GPCR) regulate Akt. Whereas growth-factor activation has been extensively studied, the regulation by GPCR's, especially gastrointestinal hormones/neurotransmitters, remains unclear. To address this area, in study effects GI hormones/neurotransmitters were investigated rat pancreatic acinar cells which are high responsive to these agents. Pancreatic acini expressed 5 7 known growth-factors stimulate phosphorylation (T308, S473) translocation. These mediated p85 PI3K. hormones increasing intracellular cAMP had similar effects. However, GI-hormones/neurotransmitters [CCK, bombesin, carbachol] activating phospholipase C (PLC) inhibited basal growth-factor-stimulated activation. Detailed studies with CCK, both physiological pathophysiological on at different concentrations, demonstrated CCK biphasic effect: low concentrations (pM) stimulating Src-dependent mechanism higher (nM) stimulated translocation, activation, de-phosphorylating resulting decreasing PI3K activity. This effect required limbs PLC-pathway protein tyrosine phosphatase, but was not p44/42 MAPK, Src or serine phosphatase. inhibition also found vivo Panc-1 cancer where it serum-mediated rescue from apoptosis. results demonstrate that as well cellular basis action can all cells. complex agents such because stimulatory inhibitory be seen, mechanisms.