Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1gene.[5][6][7] This protein is also called RhoGEF1 or p115-RhoGEF.
Rho guanine nucleotide exchange factor 1 is guanine nucleotide exchange factor (GEF) for the RhoAsmall GTPase protein.[5] Rho is a small GTPase protein that is inactive when bound to the guaninenucleotideGDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions.[8] In particular, active Rho is a major regulator of the cell actincytoskeleton.[8]
RhoGEF1 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13heterotrimeric G proteins.[9][10] The others are ARHGEF11 (also known as PDZ-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). [11][12] GPCR-regulated RhoGEF1 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. In addition to being activated by G12 or G13 G proteins, three of these four RhoGEF proteins (ARHGEF1/11/12) also function as RGS familyGTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G12/G13 alpha proteins (which are themselves GTPase proteins). This action increases the rate of G protein deactivation, limiting the time during which these RhoGEFs activate Rho.[13]
Multiple alternatively spliced transcript variants have been identified for this gene, but the full-length nature and function of some variants has not been defined.[7]
^Aasheim HC, Pedeutour F, Smeland EB (April 1997). "Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues". Oncogene. 14 (14): 1747–52. doi:10.1038/sj.onc.1200994. PMID9135076. S2CID24528606.
^ abThumkeo D, Watanabe S, Narumiya S (Oct–Nov 2013). "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology. 92 (10–11): 303–15. doi:10.1016/j.ejcb.2013.09.002. PMID24183240.
^Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, et al. (June 1998). "p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13". Science. 280 (5372): 2109–11. doi:10.1126/science.280.5372.2109. PMID9641915.
^ abHart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, et al. (June 1998). "Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13". Science. 280 (5372): 2112–4. doi:10.1126/science.280.5372.2112. PMID9641916.
^Kozasa T (April 2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sciences. 68 (19–20): 2309–17. doi:10.1016/S0024-3205(01)01020-7. PMID11358341.
