Activation of Adenylyl Cyclase by G(s):GTP G alpha (s) activates adenylate cyclase Glucagon:GCGR mediates GTP-GDP exchange Glucagon binds to Glucagon receptor PathwayStep2080 PathwayStep2076 PathwayStep2077 PathwayStep2075 PathwayStep2043 PKA activation in glucagon signalling Glucagon signaling in metabolic regulation Authored: Gopinathrao, G, 2005-04-27 21:11:16 GENE ONTOLOGYGO:0071377 Glucagon and insulin are peptide hormones released from the pancreas into the blood, that normally act in complementary fashion to stabilize blood glucose concentration. When blood glucose levels rise, insulin release stimulates glucose uptake from the blood, glucose breakdown (glycolysis), and glucose storage as glycogen. When blood glucose levels fall, glucagon release stimulates glycogen breakdown and de novo glucose synthesis (gluconeogenesis), while inhibiting glycolysis and glycogen synthesis.<br>At a molecular level, the binding of glucagon to the extracellular face of its receptor causes conformational changes in the receptor that allow the dissociation and activation of subunits Gs and Gq. The activation of Gq leads to the activation of phospholipase C, production of inositol 1,4,5-triphosphate, and subsequent release of intracellular calcium. The activation of Gs leads to activation of adenylate cyclase, an increase in intracellular cAMP levels, and activation of protein kinase A (PKA). Active PKA phosphorylates key enzymes of glycogenolysis, glycogenesis, gluconeogenesis, and glycolysis, modifying their activities. These signal transduction events, and some of their downstream consequences, are illustrated below (adapted from Jiang and Zhang, 2003). Pubmed12626323 Reactome Database ID Release 43163359 Reactome, http://www.reactome.org ReactomeREACT_1665