title: Atypical G(αi) signal transduction.
abstract: G protein signaling is an extremely complex event that is involved in almost every cellular process. As such, G protein-coupled receptors are the most commonly found type of transmembrane receptors used by cells to initiate intracellular signaling events. However, the widely accepted model of cyclical GDP-GTP exchange in response to ligand binding to 7TMRs, followed by dissociation of the G protein subunits and activation of intracellular signaling cascades, has repeatedly been challenged in recent years. Some of the exceptions that have been brought forth include signaling by a non-dissociated, rearranged heterotrimer and the existence of "reverse-mode", active G proteins that interact with active receptors. Here, we focus on G(αi/o), one of the common G(α) classes, and outline a major exception to the classical model, that of G protein coupling to RTKs. We then describe a novel concept in G(αi/o) signaling, namely that the pathways induced by agonist binding circumvent the typical signaling pathways responsive to decreases in the second messenger cAMP, via adenylyl cyclase inhibition.
authors.forename: Raissa
authors.initials: R
authors.lastname: Perrault
authors.affiliation: Canadian Centre for Agrifood Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB, Canada R2H 2A6. peterz@sbrc.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Zahradka
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D022461:Caveolins / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D050052:TRPC Cation Channels / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C502451:CCDC88A protein, human; D022461:Caveolins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008840:Microfilament Proteins; C404190:TNFAIP8 protein, human; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D033921:Vesicular Transport Proteins; D066246:ErbB Receptors; D011972:Receptor, Insulin; D040262:Receptors, Vascular Endothelial Growth Factor; D019206:GTP-Binding Protein alpha Subunits, Gi-Go