ARHGEFs (or GEFs) promote GDP/GTP exchange leading to activation of Rho proteins.
Guanine nucleotide exchange factors (ARHGEFs) modulate the activities of members of the RAS superfamily. GEFs are distinguished from other regulatory factors by their ability to interact preferentially with the nucleotide-depleted state of G proteins.
ARHGEF1 is a GEF that interacts with RHO GTPases (RHOs), members of the RAS superfamily (RASSFs) believed to be involved in cytoskeletal restructuring.
Rho-related small GTPases (RHOs) are involved in regulating signal transduction cascades from extracellular stimuli to the cell nucleus and cytoskeleton.
MCF2-like guanine nucleotide exchange factors (GEFs), such as ARHGEFs, catalyze the exchange of bound GDP for GTP on Rho-related proteins. MCF2 (or DBL) is a member of a large family of GDP-GTP exchange factors (ARHGEFs) that modulate the activity of small GTPases of the Rho family (RHOs).
GTPases of the Rho subfamily are widely involved in the myelination of the vertebrate nervous system. Rho GTPase activity is temporally and spatially regulated by a set of specific guanine nucleotide exchange factors (ARHGEFs).
Rho GTPase activation, which is mediated by guanine nucleotide exchange factors (GEFs), is tightly regulated in time and space.
Although Rho GTPases have a significant role in many biological events, they are best known for their ability to restructure the actin cytoskeleton profoundly through the activation of specific downstream effectors.
Two distinct families of GEFs for Rho GTPases have been reported so far, based on the features of their catalytic domains: firstly, the classical GEFs, which contain a Dbl homology-pleckstrin homology domain module with GEF activity, and secondly, the Dock180-related GEFs, which contain a Dock homology region-2 domain that catalyzes guanine nucleotide exchange on Rho GTPases.
The DHR-2 domain-containing GEFs have key role in a wide variety of fundamentally important biological functions, including cell migration, phagocytosis of apoptotic cells, myoblast fusion and neuronal polarization.
Members
| ARHGEF1 | ARHGEF2 | ARHGEF3 | ARHGEF4 | ARHGEF5 | ARHGEF6 |
| FGD4 |
Pathology
mutations in frabin/FGD4 Rho GTPase guanine nucleotide exchange factor (ARHGEFs) in Charcot-Marie-Tooth disease type 4H (CMT4H) with peripheral nerve demyelination (MIM.609311) (17564972)
ARHGEF3 variants in postmenopausal osteoporosis (18499081)
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
Stendel C, Roos A, Deconinck T, Pereira J, Castagner F, Niemann A, Kirschner J, Korinthenberg R, Ketelsen UP, Battaloglu E, Parman Y, Nicholson G, Ouvrier R, Seeger J, De Jonghe P, Weis J, Krüttgen A, Rudnik-Schöneborn S, Bergmann C, Suter U, Zerres K, Timmerman V, Relvas JB, Senderek J.Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4. Am J Hum Genet. 2007 Jul;81(1):158-64. PMID: 17564972