Distinct pathways of Gi- and Gq-mediated mitogen-activated protein kinase activation

摘要: Receptors that couple to the heterotrimeric G proteins, Gi or Gq, can stimulate phosphoinositide (PI) hydrolysis and mitogen-activated protein kinase (MAPK) activation. PI produces inositol 1,4,5-trisphosphate diacylglycerol, leading activation of C (PKC), which increased MAPK activity. However, relationship between in Gq signaling has not been clearly defined is subject this study. The effects several inhibitors are assessed including expression a peptide derived from carboxyl terminus beta adrenergic receptor 1 (beta ARKct), specifically blocks mediated by gamma subunits proteins (G gamma), dominant negative mutants p21ras (RasN17) p74raf-1 (N delta Raf), protein-tyrosine (PTK) cellular depletion PKC. Gi-coupled alpha 2A (AR) stimulates blocked ARKct, RasN17, N Raf, PTK inhibitors, but unaffected In contrast, stimulated Gq-coupled 1B AR M1 muscarinic cholinergic ARKct RasN17 Raf PKC depletion. These data demonstrate Gi- receptors via distinct pathways. responsible for mediating receptor-stimulated through mechanism utilizing p74raf independent mediates using p21ras-independent employing p74raf. To define role receptor-mediated activation, direct stimulation with was used. Expression resulted sensitive inhibition insensitive By comparison, gamma-mediated affected inhibitors. Together, these results