Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor - Apparent disruption of receptor signaling complexes

作者：Takesono A; Nowak MW; Cismowski M; Duzic E; Lanier SM^*

来源：Journal of Biological Chemistry, 2002, 277(16): 13827-13830.

DOI：10.1074/jbc.M201064200

The Ras-related protein, activator of G-protein signal. ing 1 (AGS1) or Dexras1, interacts with G(i)/G(o)alpha and activates heterotrimeric G-protein signaling systems independent of a G-protein-coupled receptor (GPCR). As an initial approach to further define the cellular role of AGS1 in GPCR signaling, we determined the influence of AGS1 on the regulation of G(betagamma)-regulated inwardly rectifying K+ channel (GIRK) current (I-ACh) by M-2-muscarinic receptor (M-2-MR) in Xenopus oocytes. AGS1 expression inhibited receptor-mediated current activation by >80%. Mutation of a key residue (G31V) within the G, domain involved in nucleotide binding for Ras-related proteins eliminated the action of AGS1. The inhibition of I-ACh was not overcome by increasing concentrations of the muscarinic agonist acetylcholine but was progressively lost upon injection of increasing amounts of M-2-MR cRNA. These data suggest that AGS1 may antagonize GPCR signaling by altering the pool of heterotrimeric G-proteins available for receptor coupling and/or disruption of a preformed signaling complex. Such regulation would be of particular importance for those receptors that exist precoupled to heterotrimeric G-protein and for receptors operating within signaling complexes.

• 出版日期2002-4-19