G protein specificity: traffic direction required.
This review focuses on the coupling specificity of the Galpha and Gbetagamma subunits of pertussis toxin (PTX)-sensitive G(i/o) proteins that mediate diverse signaling pathways, including regulation of ion channels and other effectors. Several lines of evidence indicate that specific combinations of G protein alpha, beta and gamma subunits are required for different receptors or receptor-effector networks, and that a higher degree of specificity for Galpha and Gbetagamma is observed in intact systems than reported in vitro. The structural determinants of receptor-G protein specificity remain incompletely understood, and involve receptor-G protein interaction domains, and perhaps other scaffolding processes. By identifying G protein specificity for individual receptor signaling pathways, ligands targeted to disrupt individual pathways of a given receptor could be developed.
Albert
Paul R
PR
Ottawa Health Research Institute, Neuroscience, University of Ottawa, 451 Smyth Road, K1H-8M5, Ottawa, ON, Canada. palbert@uottawa.ca
Robillard
Liliane
L
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry / Q000502:physiology*; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D015221:Potassium Channels / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
D015220:Calcium Channels; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D046911:Macromolecular Substances; D015221:Potassium Channels; D011956:Receptors, Cell Surface; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases