RHOs
The RHO family of small GTPases (RHOs) are involved in signal transduction through transmembrane receptors, and they are inactive in the GDP-bound form and active in the GTP-bound form.
Members of the Rho family of Ras-related GTPases (RHOs) regulate the organization of the actin cytoskeleton in response to extracellular growth factors.
Members
| RHOA | MIM.165390 | 3p21.3 |
| RHOB | MIM.165370 | 2pter-p12 |
| RHOC | MIM.165380 | 1p21-p13 |
| RHOD | MIM.605781 | 11q14.3 |
| RHOE (RND3) | MIM.602924 | - |
Like Ras proteins (RASs: HRAS, KRAS, NRAS), Rho family members appear to cycle between an inactive GDP-bound form and an active GTP-bound form.
Three major regulators of Rho activity have been identified:
ARHGDIAs (RhoGDIs), which interact with the GDP-bound Rho proteins to keep them in a resting complex
ARHGEFs (or GEFs), which promote GDP/GTP exchange leading to activation of Rho proteins
GAPs, which stimulate GTP hydrolysis and return the activated Rho protein to its inactive form.
ARHGAPs (GTPase-activating proteins), which inactivate RHO family proteins (RHOs) by stimulating their hydrolysis of GTP.
Functions
Rho GTPases control a variety of cellular processes. There are 3 subtypes of Rho GTPases in the Ras superfamily of small G proteins: RHO (MIM.165370), RAC (RAC1) (MIM.602048), and CDC42 (MIM.116952).
GTPase-activating proteins (GAPs) bind activated forms of Rho GTPases and stimulate GTP hydrolysis. Through this catalytic function, Rho GAPs negatively regulate Rho-mediated signals. GAPs may also serve as effector molecules and play a role in signaling downstream of Rho and other Ras-like GTPases.
ARHGAPs
GTPase-activating proteins (ARHGAPs), such as ARHGAP23, inactivate RHO family proteins (RHOs) by stimulating their hydrolysis of GTP.
Pathology (Examples)
mutations in Rho GTPase guanine nucleotide exchange factor (see ARHGEFs) frabin/FGD4 in peripheral nerve demyelination (#17564972#)
See also
integrin-mediated adhesion
cholesterol-enriched membrane domains
endocytosis
caveolae
caveolin-1
integrins
References
Côté JF, Vuori K. GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. Trends Cell Biol. 2007 Aug;17(8):383-93. PMID: #17765544#