Thinking Outside the RGS Box

Proteins of regulator of the G protein signaling (RGS) family contain a conserved domain, the RGS domain, that allows these proteins to serve as negative regulators of heterotrimeric guanine nucleotide-binding proteins (G proteins) by stimulating G protein intrinsic guanosine triphosphatase (GTPase) activity. Thus, RGS proteins serve as GAPs (GTPase-activating proteins). Johnson et al. provide evidence that RGS16, which has an RGS domain and can serve as a GAP for Gαi, does not require the RGS domain to inhibit Gα 13 signaling. Instead, inhibition of Gα 13 required the N-terminal domain of RGS16, which blocked the interaction of Gα 13 with its downstream effector, the guanine nucleotide exchange factor for the small GTPase Rho (p115Rho-GEF). RGS16 also altered the localization of Gα 13 such that the G protein was partially redirected to lipid rafts. Thus, RGS proteins appear able to affect G protein signaling through multiple mechanisms that allow specific interactions of a single RGS protein with different Gα subunits. E. N. Johnson, T. M. Seasholtz, A. A. Waheed, B. Kreutz, N. Suzuki, T. Kozasa, T. L. Z. Jones, J. H. Brown, K. M. Druey, RGS16 inhibits signalling through the Gα 13 -Rho axis. Nat. Cell Biol. 5 , 1095-1103 (2003). [Online Journal]