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.

[1]  A. Gilman,et al.  p115 RhoGEF, a GTPase activating protein for Gα12 and Gα13 , 1998 .

[2]  P. Sternweis,et al.  Regulation of Phospholipase D by Protein Kinase C Is Synergistic with ADP-ribosylation Factor and Independent of Protein Kinase Activity (*) , 1996, The Journal of Biological Chemistry.

[3]  C. Der,et al.  Dbl family proteins. , 1997, Biochimica et biophysica acta.

[4]  H. Hamm,et al.  An Effector Site That Stimulates G-protein GTPase in Photoreceptors (*) , 1995, The Journal of Biological Chemistry.

[5]  A. Gilman,et al.  Mammalian RGS Proteins: Barbarians at the Gate* , 1998, The Journal of Biological Chemistry.

[6]  Stefan Offermanns,et al.  Vascular System Defects and Impaired Cell Chemokinesis as a Result of Gα13 Deficiency , 1997, Science.

[7]  R. T. Miller,et al.  Purification and characterization of the alpha subunit of G13. , 1994, The Journal of biological chemistry.

[8]  Mark S. Boguski,et al.  Proteins regulating Ras and its relatives , 1993, Nature.

[9]  A. Gilman,et al.  The guanine nucleotide activating site of the regulatory component of adenylate cyclase. Identification by ligand binding. , 1982, The Journal of biological chemistry.

[10]  S. Haney,et al.  Cdc25p, the guanine nucleotide exchange factor for the Ras proteins of Saccharomyces cerevisiae, promotes exchange by stabilizing Ras in a nucleotide-free state. , 1994, The Journal of biological chemistry.

[11]  E M Ross,et al.  Regulation of phospholipase C-beta1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation. , 1996, The Journal of biological chemistry.

[12]  N. Perrimon,et al.  DRhoGEF2 encodes a member of the Dbl family of oncogenes and controls cell shape changes during gastrulation in Drosophila. , 1998, Genes & development.

[13]  G. Bollag,et al.  Identification of a Novel Guanine Nucleotide Exchange Factor for the Rho GTPase* , 1996, The Journal of Biological Chemistry.

[14]  A. Hall,et al.  Rho GTPases and the actin cytoskeleton. , 1998, Science.