title: RGS16 inhibits signalling through the G alpha 13-Rho axis.
abstract: 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.
authors.affiliation: Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases/National Institute of Health, Rockville, MD 20852, USA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Johnson
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Seasholtz
authors.forename: Abdul A
authors.initials: AA
authors.lastname: Waheed
authors.forename: Barry
authors.initials: B
authors.lastname: Kreutz
authors.forename: Nobuchika
authors.initials: N
authors.lastname: Suzuki
authors.forename: Tohru
authors.initials: T
authors.lastname: Kozasa
authors.forename: Teresa L Z
authors.initials: TL
authors.lastname: Jones
authors.forename: Joan Heller
authors.initials: JH
authors.lastname: Brown
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Druey
mesh_terms: D045744:Cell Line, Tumor; D025461:Feedback, Physiological / Q000235:genetics; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D020710:RGS Proteins; C107413:RGS16 protein; D064067:Rho Guanine Nucleotide Exchange Factors; C098799:RGS4 protein; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020741:rho GTP-Binding Proteins