title: A bifunctional Galphai/Galphas modulatory peptide that attenuates adenylyl cyclase activity.
abstract: Signaling via G-protein coupled receptors is initiated by receptor-catalyzed nucleotide exchange on Galpha subunits normally bound to GDP and Gbetagamma. Activated Galpha . GTP then regulates effectors such as adenylyl cyclase. Except for Gbetagamma, no known regulators bind the adenylyl cyclase-stimulatory subunit Galphas in its GDP-bound state. We recently described a peptide, KB-752, that binds and enhances the nucleotide exchange rate of the adenylyl cyclase-inhibitory subunit Galpha(i). Herein, we report that KB-752 binds Galpha(s) . GDP yet slows its rate of nucleotide exchange. KB-752 inhibits GTPgammaS-stimulated adenylyl cyclase activity in cell membranes, reflecting its opposing effects on nucleotide exchange by Galpha(i) and Galpha(s).
authors.affiliation: Department of Pharmacology, The University of North Carolina at Chapel Hill, 27599-7365, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Johnston
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Ramer
authors.forename: Rainer
authors.initials: R
authors.lastname: Blaesius
authors.forename: Zoey
authors.initials: Z
authors.lastname: Fredericks
authors.forename: Val J
authors.initials: VJ
authors.lastname: Watts
authors.forename: David P
authors.initials: DP
authors.lastname: Siderovski
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D002478:Cells, Cultured; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000037:antagonists & inhibitors*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; C506074:KB-752 peptide; D010455:Peptides; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs