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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Carter, Angela M. Gutowski, Stephen Sternweis, Paul C. |
| Description | Author Affiliation: Carter AM ( From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.); Gutowski S ( From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390.); Sternweis PC ( From the Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 Paul.Sternweis@UTsouthwestern.edu.) |
| Abstract | The regulator of G protein signaling homology (RH) Rho guanine nucleotide exchange factors (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PDZ-RhoGEF) contain an RH domain and are specific GEFs for the monomeric GTPase RhoA. The RH domains interact specifically with the subunits of G12 heterotrimeric GTPases. Activated G 13 modestly stimulates the exchange activity of both p115RhoGEF and leukemia-associated RhoGEF but not PDZ-RhoGEF. Because all three RH-RhoGEFs can localize to the plasma membrane upon expression of activated G 13, cellular localization of these RhoGEFs has been proposed as a mechanism for controlling their activity. We use a small molecule-regulated heterodimerization system to rapidly control the localization of RH-RhoGEFs. Acute localization of the proteins to the plasma membrane activates RhoA within minutes and to levels that are comparable with activation of RhoA by hormonal stimulation of G protein-coupled receptors. The catalytic activity of membrane-localized RhoGEFs is not dependent on activated G 13. We further show that the conserved RH domains can rewire two different RacGEFs to activate Rac1 in response to a traditional activator of RhoA. Thus, RH domains act as independent detectors for activated G 13 and are sufficient to modulate the activity of RhoGEFs by hormones via mediating their localization to substrate, membrane-associated RhoA. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 28 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-07-11 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Membrane Hormones Protein Multimerization Physiology Rho Guanine Nucleotide Exchange Factors Catalysis Chemistry Enzymology Genetics GTP-Binding Protein Alpha Subunits, G12-G13 Metabolism HeLa Cells RhoA GTP-Binding Protein Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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