Nature Cell Biology5, 1095 - 1103 (2003)
Published online: 23 November 2003; | doi:10.1038/ncb1065
RGS16 inhibits signalling through the G13−Rho axis
Eric N. Johnson1, 5, Tammy M. Seasholtz2, 5, Abdul A. Waheed3, Barry Kreutz4, Nobuchika Suzuki4, Tohru Kozasa4, Teresa L.Z. Jones3, Joan Heller Brown2
& Kirk M. Druey1
1
Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases/National Institute of Health, Rockville, MD 20852, USA.
2
Department of Pharmacology, University of California, San Diego, School of Medicine, San Diego, CA 92093, USA.
3
Metabolic Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases/National Institute of Health, Bethesda, MD 20892, USA.
4
Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
G13 stimulates the guanine nucleotide exchange factors (GEFs) for Rho, such as p115Rho-GEF1. Activated Rho induces numerous cellular responses, including actin polymerization, serum response element (SRE)-dependent gene transcription and transformation2. p115Rho-GEF contains a Regulator of G protein Signalling domain (RGS box) that confers GTPase activating protein (GAP) activity towards G12 and G13 (ref. 3). In contrast, classical RGS proteins (such as RGS16 and RGS4) exhibit RGS domain-dependent GAP activity on Gi and Gq, but not G12 or G13 (ref 4). Here, we show that RGS16 inhibits G13-mediated, RhoA-dependent reversal of stellation and SRE activation. The RGS16 amino terminus binds G13 directly, resulting in translocation of G13 to detergent-resistant membranes (DRMs) and reduced p115Rho-GEF binding. RGS4 does not bind G13 or attenuate G13-dependent responses, and neither RGS16 nor RGS4 affects G12-mediated signalling. These results elucidate a new mechanism whereby a classical RGS protein regulates G13-mediated signal transduction independently of the RGS box.
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13−Rho axis
13 stimulates the guanine nucleotide exchange factors (GEFs) for Rho, such as p115Rho-GEF
