The receptor:G-protein complex releases GDP The high affinity receptor complex binds to G-protein The receptor:G-protein complex binds GTP The receptor:G-protein complex dissociates G-protein alpha subunit is inactivated G-protein beta-gamma subunits rebind the alpha-GDP subunit PathwayStep5794 PathwayStep5795 PathwayStep5792 PathwayStep5793 PathwayStep5790 PathwayStep5791 G-protein activation Authored: Le Novere, N, Jassal, B, 2004-03-31 12:22:05 Edited: Jassal, B, 2008-11-06 10:17:49 Pubmed12184727 Pubmed15294442 Pubmed9218123 Reactome Database ID Release 43202040 Reactome, http://www.reactome.org ReactomeREACT_15457 Receptor activated heterotrimeric G proteins consist of the Galpha and the tightly associated Gbeta-gamma subunits. When a ligand binds to a G protein-coupled receptor, it stabilises a conformation with an high affinity for the G-protein bound to GDP. GDP is then exchanged for GTP on the Galpha subunit. This exchange triggers the dissociation of the Galpha subunit from the Gbeta-gamma dimer and the receptor. Galpha-GTP and Gbeta-gamma, can then modulate different signalling cascades and effector proteins, while the receptor is able to activate another G protein, resulting in an amplification cascade. The Galpha subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity, allowing it to reassociate with Gbeta-gamma and start a new cycle. Reviewed: Castagnoli, L, 2008-11-06 12:55:54