RGS16 inhibits signalling through the G alpha 13-Rho axis.
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.
Johnson
Eric N
EN
Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases/National Institute of Health, Rockville, MD 20852, USA.
Seasholtz
Tammy M
TM
Waheed
Abdul A
AA
Kreutz
Barry
B
Suzuki
Nobuchika
N
Kozasa
Tohru
T
Jones
Teresa L Z
TL
Brown
Joan Heller
JH
Druey
Kirk M
KM
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*
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