Sci. STKE, 16 January 2001
G Proteins AGS3 Frees β Subunits
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 β 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 β subunit for binding to the inactive, guanosine diphosphate (GDP)-bound state of Gαi. AGS3 was able to interact with multiple α subunits simultaneously; however, AGS3 was selective for binding Gαi1-3 and exhibited limited or undetectable binding to Gαs, Gαq, or Gα0. AGS3 inhibited binding of GTPS 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 β could increase the available pool of free β 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]
Citation: AGS3 Frees β Subunits. Sci. STKE 2001, tw3 (2001).
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