ARHGEF11
Protein-coding gene in the species Homo sapiens
Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene .[ 5] [ 6] [ 7] This protein is also called RhoGEF11 or PDZ-RhoGEF.
Function
Rho guanine nucleotide exchange factor 11 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein.[ 8] Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP . 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.[ 9] In particular, active Rho is a major regulator of the cell actin cytoskeleton .[ 9]
RhoGEF11 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins .[ 8] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). [ 10] [ 11] GPCR-regulated RhoGEF11 (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 family GTPase-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]
Two alternative transcripts encoding different isoforms have been described.[ 7]
Interactions
ARHGEF11 has been shown to interact with:
See also
References
^ a b c GRCh38: Ensembl release 89: ENSG00000132694 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041977 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ a b Rümenapp U, Blomquist A, Schwörer G, Schablowski H, Psoma A, Jakobs KH (Oct 1999). "Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member". FEBS Letters . 459 (3): 313– 8. doi :10.1016/S0014-5793(99)01270-3 . PMID 10526156 . S2CID 8529412 .
^ Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro" . DNA Research . 4 (2): 141– 50. doi :10.1093/dnares/4.2.141 . PMID 9205841 .
^ a b "Entrez Gene: ARHGEF11 Rho guanine nucleotide exchange factor (GEF) 11" .
^ a b Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS (Feb 1999). "A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho" . The Journal of Biological Chemistry . 274 (9): 5868– 79. doi :10.1074/jbc.274.9.5868 . PMID 10026210 .
^ a b Thumkeo, 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– 315. doi :10.1016/j.ejcb.2013.09.002 . PMID 24183240 .
^ Fukuhara S, Chikumi H, Gutkind JS (2001). "RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?" . Oncogene . 20 (13): 1661– 8. doi :10.1038/sj.onc.1204182 . PMID 11313914 .
^ Diviani, D; Soderling, J; Scott, JD (Nov 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation" . Journal of Biological Chemistry . 276 (47): 44247– 44257. doi :10.1074/jbc.M106629200 . PMID 11546812 .
^ Kozasa T (2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sci . 68 (19– 20): 2309– 17. doi :10.1016/S0024-3205(01)01020-7 . PMID 11358341 .
^ a b Chen, Z; Singer, WD; Danesh, SM; Sternweis, PC; Sprang, SR (Oct 2008). "Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF" . Structure . 16 (10): 1532– 1543. doi :10.1016/j.str.2008.07.009 . PMC 2586972 . PMID 18940608 .
^ a b c Perrot V, Vazquez-Prado J, Gutkind JS (Nov 2002). "Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF" . The Journal of Biological Chemistry . 277 (45): 43115– 20. doi :10.1074/jbc.M206005200 . PMID 12183458 .
^ a b Swiercz JM, Kuner R, Behrens J, Offermanns S (Jul 2002). "Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology" . Neuron . 35 (1): 51– 63. doi :10.1016/S0896-6273(02)00750-X . PMID 12123608 . S2CID 18981429 .
^ Oinuma I, Katoh H, Harada A, Negishi M (Jul 2003). "Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells" . The Journal of Biological Chemistry . 278 (28): 25671– 7. doi :10.1074/jbc.M303047200 . PMID 12730235 .
^ Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S (Sep 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 . PMID 12220504 .
Further reading
Togashi H, Nagata K, Takagishi M, Saitoh N, Inagaki M (Sep 2000). "Functions of a rho-specific guanine nucleotide exchange factor in neurite retraction. Possible role of a proline-rich motif of KIAA0380 in localization" . The Journal of Biological Chemistry . 275 (38): 29570– 8. doi :10.1074/jbc.M003726200 . PMID 10900204 .
Jackson M, Song W, Liu MY, Jin L, Dykes-Hoberg M, Lin CI, Bowers WJ, Federoff HJ, Sternweis PC, Rothstein JD (Mar 2001). "Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins" . Nature . 410 (6824): 89– 93. Bibcode :2001Natur.410...89J . doi :10.1038/35065091 . PMID 11242047 . S2CID 4381210 .
Longenecker KL, Lewis ME, Chikumi H, Gutkind JS, Derewenda ZS (Jul 2001). "Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases" . Structure . 9 (7): 559– 69. doi :10.1016/S0969-2126(01)00620-7 . PMID 11470431 .
Perrot V, Vazquez-Prado J, Gutkind JS (Nov 2002). "Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF" . The Journal of Biological Chemistry . 277 (45): 43115– 20. doi :10.1074/jbc.M206005200 . PMID 12183458 .
Driessens MH, Olivo C, Nagata K, Inagaki M, Collard JG (Oct 2002). "B plexins activate Rho through PDZ-RhoGEF" . FEBS Letters . 529 (2– 3): 168– 72. doi :10.1016/S0014-5793(02)03323-9 . PMID 12372594 .
Nakayama M, Kikuno R, Ohara O (Nov 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs" . Genome Research . 12 (11): 1773– 84. doi :10.1101/gr.406902 . PMC 187542 . PMID 12421765 .
Barac A, Basile J, Vázquez-Prado J, Gao Y, Zheng Y, Gutkind JS (Feb 2004). "Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor" . The Journal of Biological Chemistry . 279 (7): 6182– 9. doi :10.1074/jbc.M309579200 . PMID 14625312 .
Davidkova G, McCullumsmith RE, Meador-Woodruff JH (Nov 2003). "Expression of ARHGEF11 mRNA in schizophrenic thalamus" (PDF) . Annals of the New York Academy of Sciences . 1003 (1): 375– 7. Bibcode :2003NYASA1003..375D . doi :10.1196/annals.1300.030 . hdl :2027.42/74092 . PMID 14684465 . S2CID 8158533 .
Banerjee J, Wedegaertner PB (Apr 2004). "Identification of a novel sequence in PDZ-RhoGEF that mediates interaction with the actin cytoskeleton" . Molecular Biology of the Cell . 15 (4): 1760– 75. doi :10.1091/mbc.E03-07-0527 . PMC 379273 . PMID 14742719 .
Wang Q, Liu M, Kozasa T, Rothstein JD, Sternweis PC, Neubig RR (Jul 2004). "Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells" . The Journal of Biological Chemistry . 279 (28): 28831– 4. doi :10.1074/jbc.C400105200 . PMID 15143072 .
Guo X, Li Y, Peng K, Hu Y, Li C, Xia B, Jin C (Nov 2005). "Solution structures and backbone dynamics of arsenate reductase from Bacillus subtilis: reversible conformational switch associated with arsenate reduction" . The Journal of Biological Chemistry . 280 (47): 39601– 8. doi :10.1074/jbc.M508132200 . PMID 16192272 .
Longhurst DM, Watanabe M, Rothstein JD, Jackson M (Apr 2006). "Interaction of PDZRhoGEF with microtubule-associated protein 1 light chains: link between microtubules, actin cytoskeleton, and neuronal polarity" . The Journal of Biological Chemistry . 281 (17): 12030– 40. doi :10.1074/jbc.M513756200 . PMID 16478718 .
Gu J, Wu X, Dong Q, Romeo MJ, Lin X, Gutkind JS, Berman DM (Jun 2006). "A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans" . Cancer . 106 (12): 2716– 24. doi :10.1002/cncr.21944 . PMID 16691626 .
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks" . Cell . 127 (3): 635– 48. doi :10.1016/j.cell.2006.09.026 . PMID 17081983 . S2CID 7827573 .
Ma L, Hanson RL, Que LN, Cali AM, Fu M, Mack JL, Infante AM, Kobes S, Bogardus C, Shuldiner AR, Baier LJ (May 2007). "Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians" . Diabetes . 56 (5): 1454– 9. doi :10.2337/db06-0640 . PMID 17287471 .
External links
PDB gallery
1htj : STRUCTURE OF THE RGS-LIKE DOMAIN FROM PDZ-RHOGEF
1xcg : Crystal Structure of Human RhoA in complex with DH/PH fragment of PDZRHOGEF
2dls : Solution structure of the PDZ domain of human Rho guanine nucleotide exchange factor 11