G PROTEINS AGS3 Frees ß Subunits

Abstract:

G proteins are heterotrimeric proteins that are activated when guanosine triphosphate (GTP) binds the subunit, promoting the dissociation of the complex into a GTP-bound subunit and a free ß 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 ß subunit for binding to the inactive, guanosine diphosphate (GDP)-bound state of G_i. AGS3 was able to interact with multiple subunits simultaneously; however, AGS3 was selective for binding G_i1-3 and exhibited limited or undetectable binding to G_s, G_q, or G₀. AGS3 inhibited binding of GTPS to the a subunit suggesting that AGS3 may stabilize the GDP-bound or nucleotide-free form of the subunit. This effect on the subunit along with the ability to compete for the binding of ß could increase the available pool of free ß 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]