Login
Login

ARHGEF11

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene.{{cite journal | vauthors = Rümenapp U, Blomquist A, Schwörer G, Schablowski H, Psoma A, Jakobs KH | title = Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member | journal = FEBS Letters | volume = 459 | issue = 3 | pages = 313–8 | date = Oct 1999 | pmid = 10526156 | doi = 10.1016/S0014-5793(99)01270-3 | s2cid = 8529412 }}{{cite journal | vauthors = Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = 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 | journal = DNA Research | volume = 4 | issue = 2 | pages = 141–50 | date = Apr 1997 | pmid = 9205841 | doi = 10.1093/dnares/4.2.141 | doi-access = free }}{{cite web | title = Entrez Gene: ARHGEF11 Rho guanine nucleotide exchange factor (GEF) 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9826}} 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.{{cite journal | vauthors = Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS | title = A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho | journal = The Journal of Biological Chemistry | volume = 274 | issue = 9 | pages = 5868–79 | date = Feb 1999 | pmid = 10026210 | doi = 10.1074/jbc.274.9.5868 | doi-access = free }} 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.{{cite journal |last1=Thumkeo |first1=D |last2=Watanabe |first2=S |last3=Narumiya |first3=S |date= Oct–Nov 2013 |title=Physiological roles of Rho and Rho effectors in mammals |journal=European Journal of Cell Biology |volume=92 |issue=10–11 |pages=303–315 |doi=10.1016/j.ejcb.2013.09.002 |pmid=24183240 }}

In particular, active Rho is a major regulator of the cell actin cytoskeleton.

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. The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). {{cite journal | vauthors = Fukuhara S, Chikumi H, Gutkind JS | title = RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho? | journal = Oncogene | volume = 20 | issue = 13 | pages = 1661–8 | year = 2001 | pmid = 11313914 | doi = 10.1038/sj.onc.1204182 | doi-access = free }}{{cite journal |last1= Diviani |first1=D |last2=Soderling |first2=J |last3=Scott |first3=JD |date= Nov 2001 |title=AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation |journal= Journal of Biological Chemistry |volume=276 |issue=47 |pages=44247–44257 |doi=10.1074/jbc.M106629200 |pmid=11546812 |doi-access=free }} 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.{{cite journal | vauthors = Kozasa T | title = Regulation of G protein-mediated signal transduction by RGS proteins | journal = Life Sci. | volume = 68 | issue = 19–20 | pages = 2309–17 | year = 2001 | pmid = 11358341 | doi = 10.1016/S0024-3205(01)01020-7 }}

Two alternative transcripts encoding different isoforms have been described.

Interactions

ARHGEF11 has been shown to interact with:

  • GNA12{{cite journal |last1=Chen |first1=Z |last2=Singer |first2=WD |last3=Danesh |first3=SM |last4=Sternweis |first4=PC |last5=Sprang |first5=SR |date=Oct 2008 |title=Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF |journal=Structure |volume=16 |issue=10 |pages=1532–1543 |doi=10.1016/j.str.2008.07.009 |pmid=18940608 |pmc=2586972 }}
  • GNA13
  • PLXNB1,{{cite journal | vauthors = Oinuma I, Katoh H, Harada A, Negishi M | title = Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells | journal = The Journal of Biological Chemistry | volume = 278 | issue = 28 | pages = 25671–7 | date = Jul 2003 | pmid = 12730235 | doi = 10.1074/jbc.M303047200 | doi-access = free }}{{cite journal | vauthors = Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S | title = Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors | journal = Biochemical and Biophysical Research Communications | volume = 297 | issue = 1 | pages = 32–7 | date = Sep 2002 | pmid = 12220504 | doi = 10.1016/S0006-291X(02)02122-8 }}
  • PLXNB2{{cite journal | vauthors = Perrot V, Vazquez-Prado J, Gutkind JS | title = Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF | journal = The Journal of Biological Chemistry | volume = 277 | issue = 45 | pages = 43115–20 | date = Nov 2002 | pmid = 12183458 | doi = 10.1074/jbc.M206005200 | doi-access = free }}{{cite journal | vauthors = Swiercz JM, Kuner R, Behrens J, Offermanns S | title = Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology | journal = Neuron | volume = 35 | issue = 1 | pages = 51–63 | date = Jul 2002 | pmid = 12123608 | doi = 10.1016/S0896-6273(02)00750-X | s2cid = 18981429 | doi-access = free }}
  • PLXNB3,
  • RHOA

See also

References

{{reflist}}

Further reading

{{refbegin | 2}}

  • {{cite journal | vauthors = Togashi H, Nagata K, Takagishi M, Saitoh N, Inagaki M | title = Functions of a rho-specific guanine nucleotide exchange factor in neurite retraction. Possible role of a proline-rich motif of KIAA0380 in localization | journal = The Journal of Biological Chemistry | volume = 275 | issue = 38 | pages = 29570–8 | date = Sep 2000 | pmid = 10900204 | doi = 10.1074/jbc.M003726200 | doi-access = free }}
  • {{cite journal | vauthors = Jackson M, Song W, Liu MY, Jin L, Dykes-Hoberg M, Lin CI, Bowers WJ, Federoff HJ, Sternweis PC, Rothstein JD | title = Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins | journal = Nature | volume = 410 | issue = 6824 | pages = 89–93 | date = Mar 2001 | pmid = 11242047 | doi = 10.1038/35065091 | bibcode = 2001Natur.410...89J | s2cid = 4381210 | doi-access = free }}
  • {{cite journal | vauthors = Longenecker KL, Lewis ME, Chikumi H, Gutkind JS, Derewenda ZS | title = Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases | journal = Structure | volume = 9 | issue = 7 | pages = 559–69 | date = Jul 2001 | pmid = 11470431 | doi = 10.1016/S0969-2126(01)00620-7 | doi-access = free }}
  • {{cite journal | vauthors = Perrot V, Vazquez-Prado J, Gutkind JS | title = Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF | journal = The Journal of Biological Chemistry | volume = 277 | issue = 45 | pages = 43115–20 | date = Nov 2002 | pmid = 12183458 | doi = 10.1074/jbc.M206005200 | doi-access = free }}
  • {{cite journal | vauthors = Driessens MH, Olivo C, Nagata K, Inagaki M, Collard JG | title = B plexins activate Rho through PDZ-RhoGEF | journal = FEBS Letters | volume = 529 | issue = 2–3 | pages = 168–72 | date = Oct 2002 | pmid = 12372594 | doi = 10.1016/S0014-5793(02)03323-9 | doi-access = free }}
  • {{cite journal | vauthors = Nakayama M, Kikuno R, Ohara O | title = Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs | journal = Genome Research | volume = 12 | issue = 11 | pages = 1773–84 | date = Nov 2002 | pmid = 12421765 | pmc = 187542 | doi = 10.1101/gr.406902 }}
  • {{cite journal | vauthors = Barac A, Basile J, Vázquez-Prado J, Gao Y, Zheng Y, Gutkind JS | title = Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor | journal = The Journal of Biological Chemistry | volume = 279 | issue = 7 | pages = 6182–9 | date = Feb 2004 | pmid = 14625312 | doi = 10.1074/jbc.M309579200 | doi-access = free }}
  • {{cite journal | vauthors = Davidkova G, McCullumsmith RE, Meador-Woodruff JH | title = Expression of ARHGEF11 mRNA in schizophrenic thalamus | journal = Annals of the New York Academy of Sciences | volume = 1003 | pages = 375–7 | date = Nov 2003 | issue = 1 | pmid = 14684465 | doi = 10.1196/annals.1300.030 | bibcode = 2003NYASA1003..375D | hdl = 2027.42/74092 | s2cid = 8158533 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/74092/1/annals.1300.030.pdf | hdl-access = free }}
  • {{cite journal | vauthors = Banerjee J, Wedegaertner PB | title = Identification of a novel sequence in PDZ-RhoGEF that mediates interaction with the actin cytoskeleton | journal = Molecular Biology of the Cell | volume = 15 | issue = 4 | pages = 1760–75 | date = Apr 2004 | pmid = 14742719 | pmc = 379273 | doi = 10.1091/mbc.E03-07-0527 }}
  • {{cite journal | vauthors = Wang Q, Liu M, Kozasa T, Rothstein JD, Sternweis PC, Neubig RR | title = Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 28 | pages = 28831–4 | date = Jul 2004 | pmid = 15143072 | doi = 10.1074/jbc.C400105200 | doi-access = free }}
  • {{cite journal | vauthors = Guo X, Li Y, Peng K, Hu Y, Li C, Xia B, Jin C | title = Solution structures and backbone dynamics of arsenate reductase from Bacillus subtilis: reversible conformational switch associated with arsenate reduction | journal = The Journal of Biological Chemistry | volume = 280 | issue = 47 | pages = 39601–8 | date = Nov 2005 | pmid = 16192272 | doi = 10.1074/jbc.M508132200 | doi-access = free }}
  • {{cite journal | vauthors = Longhurst DM, Watanabe M, Rothstein JD, Jackson M | title = Interaction of PDZRhoGEF with microtubule-associated protein 1 light chains: link between microtubules, actin cytoskeleton, and neuronal polarity | journal = The Journal of Biological Chemistry | volume = 281 | issue = 17 | pages = 12030–40 | date = Apr 2006 | pmid = 16478718 | doi = 10.1074/jbc.M513756200 | doi-access = free }}
  • {{cite journal | vauthors = Gu J, Wu X, Dong Q, Romeo MJ, Lin X, Gutkind JS, Berman DM | title = A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans | journal = Cancer | volume = 106 | issue = 12 | pages = 2716–24 | date = Jun 2006 | pmid = 16691626 | doi = 10.1002/cncr.21944 | doi-access = free }}
  • {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
  • {{cite journal | vauthors = Ma L, Hanson RL, Que LN, Cali AM, Fu M, Mack JL, Infante AM, Kobes S, Bogardus C, Shuldiner AR, Baier LJ | title = 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 | journal = Diabetes | volume = 56 | issue = 5 | pages = 1454–9 | date = May 2007 | pmid = 17287471 | doi = 10.2337/db06-0640 | doi-access = free }}

{{refend}}

External links

  • {{UCSC gene info|ARHGEF11}}

{{PDB Gallery|geneid=9826}}