Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13.
Signaling pathways that link extracellular factors to activation of the monomeric guanosine triphosphatase (GTPase) Rho control cytoskeletal rearrangements and cell growth. Heterotrimeric guanine nucleotide-binding proteins (G proteins) participate in several of these pathways, although their mechanisms are unclear. The GTPase activities of two G protein alpha subunits, Galpha12 and Galpha13, are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated Galpha13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho. In contrast, activated Galpha12 inhibited stimulation by Galpha13. Thus, p115 RhoGEF can directly link heterotrimeric G protein alpha subunits to regulation of Rho.
Hart
M J
MJ
Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
Jiang
X
X
Kozasa
T
T
Roscoe
W
W
Singer
W D
WD
Gilman
A G
AG
Sternweis
P C
PC
Bollag
G
G
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D005459:Fluorides / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
D017607:Aluminum Compounds; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; C050992:tetrafluoroaluminate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D005459:Fluorides