AGS3 Frees βγ Subunits

Abstract

G proteins are heterotrimeric proteins that are activated when guanosine triphosphate (GTP) binds the α subunit, promoting the dissociation of the complex into a GTP-bound α subunit and a free βγ subunit, each of which can regulate downstream signaling events. Extracellular signals regulate this process through interaction with G protein-coupled receptors in the plasma membrane. However, intracellular regulators of G protein signaling are also being identified. Bernard et al. characterized biochemically how activator of G protein signaling 3 (AGS3) is able to enhance G protein signaling in the absence of receptor activation. In vitro binding assays showed that AGS3 competes with the βγ subunit for binding to the inactive, guanosine diphosphate (GDP)-bound state of Gα i . AGS3 was able to interact with multiple α subunits simultaneously; however, AGS3 was selective for binding Gα i1-3 and exhibited limited or undetectable binding to Gα s , Gα q , or Gα 0 . AGS3 inhibited binding of GTPγS to the a subunit suggesting that AGS3 may stabilize the GDP-bound or nucleotide-free form of the α subunit. This effect on the α subunit along with the ability to compete for the binding of βγ could increase the available pool of free βγ subunits that can activate downstream signaling pathways. M. L. Bernard, Y. K. Peterson, P. Chung, J. Jourdan, S. M. Lanier, Selective interaction of AGS3 with G-proteins and the influence of AGS3 on the activation state of G-proteins. J. Biol. Chem. 276 , 1585-1593 (2001). [Abstract] [Full Text]