RGS16 inhibits signalling through the G alpha 13-Rho axis

• Published in: Nature cell biology Vol. 5; no. 12; pp. 1095 - 1103
• Main Authors: Johnson, Eric N, Seasholtz, Tammy M, Waheed, Abdul A, Kreutz, Barry, Suzuki, Nobuchika, Kozasa, Tohru, Jones, Teresa L Z, Brown, Joan Heller, Druey, Kirk M
• Format: Journal Article
• Language: English
• Published: England 01-12-2003
• Subjects: Cell Line, Tumor; Feedback, Physiological - genetics; Gene Expression Regulation - genetics; Genes, Regulator - genetics; GTP-Binding Protein alpha Subunits, G12-G13 - metabolism; guanine nucleotide exchange factor; Guanine Nucleotide Exchange Factors - metabolism; Humans; Protein Binding - genetics; Protein Structure, Tertiary - genetics; Proteins - metabolism; RGS Proteins - metabolism; RGS16 protein; rho GTP-Binding Proteins - metabolism; Rho Guanine Nucleotide Exchange Factors; Rho protein; Signal Transduction - physiology
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb1065

G alpha 13 stimulates the guanine nucleotide exchange factors (GEFs) for Rho, such as p115Rho-GEF. Activated Rho induces numerous cellular responses, including actin polymerization, serum response element (SRE)-dependent gene transcription and transformation. p115Rho-GEF contains a Regulator of G protein Signalling domain (RGS box) that confers GTPase activating protein (GAP) activity towards G alpha 12 and G alpha 13 (ref. 3). In contrast, classical RGS proteins (such as RGS16 and RGS4) exhibit RGS domain-dependent GAP activity on G alpha i and G alpha q, but not G alpha 12 or G alpha 13 (ref 4). Here, we show that RGS16 inhibits G alpha 13-mediated, RhoA-dependent reversal of stellation and SRE activation. The RGS16 amino terminus binds G alpha 13 directly, resulting in translocation of G alpha 13 to detergent-resistant membranes (DRMs) and reduced p115Rho-GEF binding. RGS4 does not bind G alpha 13 or attenuate G alpha 13-dependent responses, and neither RGS16 nor RGS4 affects G alpha 12-mediated signalling. These results elucidate a new mechanism whereby a classical RGS protein regulates G alpha 13-mediated signal transduction independently of the RGS box.