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Science 26 June 1998:
Vol. 280. no. 5372, pp. 2112 - 2114
DOI: 10.1126/science.280.5372.2112
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Reports

Direct Stimulation of the Guanine Nucleotide Exchange Activity of p115 RhoGEF by Galpha 13

Matthew J. Hart, * Xuejun Jiang, * Tohru Kozasa, William Roscoe, William D. Singer, Alfred G. Gilman, Paul C. Sternweis, dagger Gideon Bollag dagger

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, Galpha 12 and Galpha 13, are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated Galpha 13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho. In contrast, activated Galpha 12 inhibited stimulation by Galpha 13. Thus, p115 RhoGEF can directly link heterotrimeric G protein alpha  subunits to regulation of Rho.

M. J. Hart, W. Roscoe, G. Bollag, Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA.
X. Jiang, T. Kozasa, W. D. Singer, A. G. Gilman, P. C. Sternweis, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9041, USA.
*   These authors contributed equally to the work.

dagger    To whom correspondence should be addressed. E-mail: sternwei{at}utsw.swmed.edu (P.C.S.) and bollag{at}onyx-pharm.com (B.G.).

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D. M. Yau, N. Yokoyama, Y. Goshima, Z. K. Siddiqui, S. S. Siddiqui, and T. Kozasa (2003)
PNAS 100, 14748-14753
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Insights into G Protein Structure, Function, and Regulation.
T. M. Cabrera-Vera, J. Vanhauwe, T. O. Thomas, M. Medkova, A. Preininger, M. R. Mazzoni, and H. E. Hamm (2003)
Endocr. Rev. 24, 765-781
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Common Signaling Pathways Link Activation of Murine PAR-1, LPA, and S1P Receptors to Proliferation of Astrocytes.
S. D. Sorensen, O. Nicole, R. D. Peavy, L. M. Montoya, C. J. Lee, T. J. Murphy, S. F. Traynelis, and J. R. Hepler (2003)
Mol. Pharmacol. 64, 1199-1209
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CCK-A receptor activates RhoA through G{alpha}12/13 in NIH3T3 cells.
S. L. Le Page, Y. Bi, and J. A. Williams (2003)
Am J Physiol Cell Physiol 285, C1197-C1206
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