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Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12gene.[5][6][7] This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG).
Function
Rho guanine nucleotide exchange factor 12 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]
RhoGEF12 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] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF) and AKAP13 (also known as ARHGEF13 and Lbc). [10][11] GPCR-regulated RhoGEF12 (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.[12]
^ abThumkeo D, Watanabe S, Narumiya S (October–November 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 (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.
^Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, et al. (September 2002). "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochemical and Biophysical Research Communications. 297 (1): 32–7. doi:10.1016/S0006-291X(02)02122-8. PMID12220504.
Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, et al. (September 2002). "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochemical and Biophysical Research Communications. 297 (1): 32–7. doi:10.1016/S0006-291X(02)02122-8. PMID12220504.