The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ARHGEF2  -  Rho/Rac guanine nucleotide exchange factor...

Homo sapiens

Synonyms: GEF, GEF-H1, GEFH1, Guanine nucleotide exchange factor H1, KIAA0651, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ARHGEF2

  • Herein, we show that the hematopoietic-specific GEF VAV1 is ectopically expressed in primary pancreatic adenocarcinomas due to demethylation of the gene promoter [1].
  • Mutations in ALS2, carrying three putative guanine exchange factor (GEF) domains, are causative for a juvenile, autosomal recessive form of amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, and infantile-ascending hereditary spastic paralysis [2].
  • For example, the Legionella protein RalF was shown previously to be a Dot/Icm substrate that functions as a guanine nucleotide exchange factor (GEF) for the Arf family of eukaryotic small GTP-binding proteins [3].
  • We observed a marked increase in the expression of Vav3, a Rho GTPase guanine nucleotide exchange factor (GEF), during the progression of human prostate cancer LNCaP cells to the androgen-independent derivative, LNCaP-R1 [4].
  • SopE2, a Salmonella guanine nucleotide exchange factor (GEF), is also involved in intestinal inflammation [5].

Psychiatry related information on ARHGEF2

  • METHODS: Behavioral measures, including prepulse inhibition (PPI) and total locomotor activity, after amphetamine exposure were assessed at postnatal day 20 (P20) (prepuberty), P40 (puberty), P60 (postpuberty), and P80 (adulthood) in animals previously exposed to allopregnanolone (10 mg/kg) on P2 and P5 [6].

High impact information on ARHGEF2

  • RhoA and hence to ROK through a mechanism involving association of GEF, RhoA, and ROK in multimolecular complexes at the lipid cell membrane [7].
  • Here, we show that the catalytic core of the Rab GEF Rabex-5 has a tandem architecture consisting of a Vps9 domain stabilized by an indispensable helical bundle [8].
  • RCC1 (regulator of chromosome condensation), a beta propeller chromatin-bound protein, is the guanine nucleotide exchange factor (GEF) for the nuclear GTP binding protein Ran [9].
  • Based on the available structural and biochemical evidence, we present a unified scenario for the GEF mechanism where interaction of the P loop lysine with an acidic residue is a crucial element for the overall reaction [9].
  • Free RF3 is in vivo stably bound to GDP, and ribosomes in complex with RF1 or RF2 act as guanine nucleotide exchange factors (GEF) [10].

Biological context of ARHGEF2


Anatomical context of ARHGEF2

  • GEF-H1 mutants that are deficient in microtubule binding have higher activity levels than microtubule-bound forms [11].
  • Overexpression of GEF-H1 in COS-7 cells results in induction of membrane ruffles [14].
  • In this study, we provide evidence that the Rho family GEF, Vav-2, is present in cytotoxic lymphocytes, and becomes tyrosine phosphorylated after the cross-linking of activating receptors on cytotoxic lymphocytes and during the generation of cell-mediated killing [16].
  • We report that the Rac1-GEF Tiam1 is present in dendrites and spines and is required for their development [17].
  • Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin [18].

Associations of ARHGEF2 with chemical compounds

  • The chemical compound NSC23766 was identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification [19].
  • Here we identify a region in the carboxyl terminus of GEF-H1 that is important for suppression of its guanine nucleotide exchange activity by microtubules [13].
  • Moreover, we found GEFH1 associated with RhoB, and DN-GEFH1 or GEFH1's RNAi suppressed the LPS-mediated RhoB activation and MHCII surface expression [20].
  • We propose that CalDAG-GEF proteins have a critical neuronal function in determining the relative activation of Ras and Rap1 signaling induced by Ca2+ and DAG mobilization [21].
  • The GDP dissociation rates of the GTPases could be further stimulated by GEF upon removal of bound Mg(2+), indicating that the GEF-catalyzed nucleotide exchange involves a Mg(2+)-independent as well as a Mg(2+)-dependent mechanism [22].
  • The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity [23].

Physical interactions of ARHGEF2

  • The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines [17].

Enzymatic interactions of ARHGEF2


Regulatory relationships of ARHGEF2

  • In contrast, a similar mutant of the Rac GEF beta-PIX fails to inhibit ARNO-induced Rac activation or motility [25].
  • Cingulin binding inhibits RhoA activation and signaling, suggesting that the increase in cingulin expression in confluent cells causes downregulation of RhoA by inhibiting GEF-H1/Lfc [26].
  • We demonstrated that AKAP-Lbc Rho-GEF activity is stimulated by the alpha subunit of the heterotrimeric G protein G12 [27].
  • Activation of endogenous Rac1 by expression of constitutively active Rac-guanine nucleotide exchange factor (GEF) derivatives was sufficient to induce high level NADPH oxidase activity in COS(phox) cells [28].

Other interactions of ARHGEF2

  • Furthermore, we conclude that the catalytic activity of Epac1 is constrained by a direct interaction between GEF and high affinity cAMP binding domains in the absence of cAMP [29].
  • G alpha 13 stimulates the guanine nucleotide exchange factors (GEFs) for Rho, such as p115Rho-GEF [30].
  • The results suggest that GEF facilitates nucleotide exchange by destabilizing both bound nucleotide and Mg(2+), whereas RhoGAP utilizes the Mg(2+) cofactor to achieve high catalytic efficiency and specificity [22].
  • The Tgat cDNA encoded a protein product consisting of the Rho-guanosine nucleotide exchange factor (GEF) domain of a multifunctional protein, TRIO, and a unique C-terminal 15-amino acid sequence, which were derived from the exons 38-46 of the Trio gene and a novel exon located downstream of its last exon (exon 58), respectively [31].
  • C-terminally truncated MR-GEF, lacking the GEF catalytic domain, retained its ability to bind M-Ras-GTP, suggesting that the RA domain is important for this interaction [32].

Analytical, diagnostic and therapeutic context of ARHGEF2

  • Immunofluorescence reveals that GEF-H1 colocalizes with microtubules through the carboxyl-terminal coiled-coil domain [14].
  • Primary sequence analysis revealed that it has the appearance of a natural chimera between a myosin motor domain and a guanine nucleotide exchange factor (GEF) domain for Rho GTPases [33].
  • Furthermore, reverse transcriptase-polymerase chain reaction and immunoreplica analysis indicate that ARNO, a member of the brefeldin A-insensitive ARF-GEF family, is expressed and predominantly localized in the cytosol and in the plasma membrane of chromaffin cells [34].
  • ECG estimation of REF from a modified Palmeri's equation showed a better correlation with radionuclide REF than did GEF derived from the standard Palmeri's equation: anterior MI; r = 0.90 vs r = 0.82, inferior MI; r = 0.84 vs r = 0.69, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[35]
  • METHODS: The flop:flip ratio and expression levels of GluR1-4 from postnatal day 8 (P8) to P40 were calculated using quantitative real-time polymerase chain reaction (PCR) analysis and immunoblot analysis [36].


  1. Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis. Fernandez-Zapico, M.E., Gonzalez-Paz, N.C., Weiss, E., Savoy, D.N., Molina, J.R., Fonseca, R., Smyrk, T.C., Chari, S.T., Urrutia, R., Billadeau, D.D. Cancer Cell (2005) [Pubmed]
  2. Unstable mutants in the peripheral endosomal membrane component ALS2 cause early-onset motor neuron disease. Yamanaka, K., Vande Velde, C., Eymard-Pierre, E., Bertini, E., Boespflug-Tanguy, O., Cleveland, D.W. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. A yeast genetic system for the identification and characterization of substrate proteins transferred into host cells by the Legionella pneumophila Dot/Icm system. Campodonico, E.M., Chesnel, L., Roy, C.R. Mol. Microbiol. (2005) [Pubmed]
  4. Vav3, a Rho GTPase Guanine Nucleotide Exchange Factor, Increases during Progression to Androgen Independence in Prostate Cancer Cells and Potentiates Androgen Receptor Transcriptional Activity. Lyons, L.S., Burnstein, K.L. Mol. Endocrinol. (2006) [Pubmed]
  5. Cooperative interactions between flagellin and SopE2 in the epithelial interleukin-8 response to Salmonella enterica serovar typhimurium infection. Huang, F.C., Werne, A., Li, Q., Galyov, E.E., Walker, W.A., Cherayil, B.J. Infect. Immun. (2004) [Pubmed]
  6. Neonatal neurosteroid administration results in development-specific alterations in prepulse inhibition and locomotor activity: neurosteroids alter prepulse inhibition and locomotor activity. Gizerian, S.S., Moy, S.S., Lieberman, J.A., Grobin, A.C. Psychopharmacology (Berl.) (2006) [Pubmed]
  7. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Somlyo, A.P., Somlyo, A.V. Physiol. Rev. (2003) [Pubmed]
  8. Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5. Delprato, A., Merithew, E., Lambright, D.G. Cell (2004) [Pubmed]
  9. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Renault, L., Kuhlmann, J., Henkel, A., Wittinghofer, A. Cell (2001) [Pubmed]
  10. A posttermination ribosomal complex is the guanine nucleotide exchange factor for peptide release factor RF3. Zavialov, A.V., Buckingham, R.H., Ehrenberg, M. Cell (2001) [Pubmed]
  11. Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Krendel, M., Zenke, F.T., Bokoch, G.M. Nat. Cell Biol. (2002) [Pubmed]
  12. Isolation and characterization of complementary DNA to proliferating cell nucleolar antigen P40. Reddy, A.B., Chatterjee, A., Rothblum, L.I., Black, A., Busch, H. Cancer Res. (1989) [Pubmed]
  13. p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor. Zenke, F.T., Krendel, M., DerMardirossian, C., King, C.C., Bohl, B.P., Bokoch, G.M. J. Biol. Chem. (2004) [Pubmed]
  14. Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. Ren, Y., Li, R., Zheng, Y., Busch, H. J. Biol. Chem. (1998) [Pubmed]
  15. Influence of human Ect2 depletion and overexpression on cleavage furrow formation and abscission. Chalamalasetty, R.B., Hümmer, S., Nigg, E.A., Silljé, H.H. J. Cell. Sci. (2006) [Pubmed]
  16. The Rho family guanine nucleotide exchange factor Vav-2 regulates the development of cell-mediated cytotoxicity. Billadeau, D.D., Mackie, S.M., Schoon, R.A., Leibson, P.J. J. Exp. Med. (2000) [Pubmed]
  17. The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines. Tolias, K.F., Bikoff, J.B., Burette, A., Paradis, S., Harrar, D., Tavazoie, S., Weinberg, R.J., Greenberg, M.E. Neuron (2005) [Pubmed]
  18. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Penzes, P., Beeser, A., Chernoff, J., Schiller, M.R., Eipper, B.A., Mains, R.E., Huganir, R.L. Neuron (2003) [Pubmed]
  19. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Gao, Y., Dickerson, J.B., Guo, F., Zheng, J., Zheng, Y. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. TRIF-GEFH1-RhoB pathway is involved in MHCII expression on dendritic cells that is critical for CD4 T-cell activation. Kamon, H., Kawabe, T., Kitamura, H., Lee, J., Kamimura, D., Kaisho, T., Akira, S., Iwamatsu, A., Koga, H., Murakami, M., Hirano, T. EMBO J. (2006) [Pubmed]
  21. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Kawasaki, H., Springett, G.M., Toki, S., Canales, J.J., Harlan, P., Blumenstiel, J.P., Chen, E.J., Bany, I.A., Mochizuki, N., Ashbacher, A., Matsuda, M., Housman, D.E., Graybiel, A.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  22. The role of Mg2+ cofactor in the guanine nucleotide exchange and GTP hydrolysis reactions of Rho family GTP-binding proteins. Zhang, B., Zhang, Y., Wang, Z., Zheng, Y. J. Biol. Chem. (2000) [Pubmed]
  23. GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Birkenfeld, J., Nalbant, P., Bohl, B.P., Pertz, O., Hahn, K.M., Bokoch, G.M. Dev. Cell (2007) [Pubmed]
  24. Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1. Kiyono, M., Kato, J., Kataoka, T., Kaziro, Y., Satoh, T. J. Biol. Chem. (2000) [Pubmed]
  25. The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1. Santy, L.C., Ravichandran, K.S., Casanova, J.E. Curr. Biol. (2005) [Pubmed]
  26. Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Aijaz, S., D'Atri, F., Citi, S., Balda, M.S., Matter, K. Dev. Cell (2005) [Pubmed]
  27. Anchoring of both PKA and 14-3-3 inhibits the Rho-GEF activity of the AKAP-Lbc signaling complex. Diviani, D., Abuin, L., Cotecchia, S., Pansier, L. EMBO J. (2004) [Pubmed]
  28. Rac activation induces NADPH oxidase activity in transgenic COSphox cells, and the level of superoxide production is exchange factor-dependent. Price, M.O., Atkinson, S.J., Knaus, U.G., Dinauer, M.C. J. Biol. Chem. (2002) [Pubmed]
  29. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. de Rooij, J., Rehmann, H., van Triest, M., Cool, R.H., Wittinghofer, A., Bos, J.L. J. Biol. Chem. (2000) [Pubmed]
  30. RGS16 inhibits signalling through the G alpha 13-Rho axis. Johnson, E.N., Seasholtz, T.M., Waheed, A.A., Kreutz, B., Suzuki, N., Kozasa, T., Jones, T.L., Brown, J.H., Druey, K.M. Nat. Cell Biol. (2003) [Pubmed]
  31. An alternative transcript derived from the trio locus encodes a guanosine nucleotide exchange factor with mouse cell-transforming potential. Yoshizuka, N., Moriuchi, R., Mori, T., Yamada, K., Hasegawa, S., Maeda, T., Shimada, T., Yamada, Y., Kamihira, S., Tomonaga, M., Katamine, S. J. Biol. Chem. (2004) [Pubmed]
  32. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. Rebhun, J.F., Castro, A.F., Quilliam, L.A. J. Biol. Chem. (2000) [Pubmed]
  33. The tail domain of myosin M catalyses nucleotide exchange on Rac1 GTPases and can induce actin-driven surface protrusions. Geissler, H., Ullmann, R., Soldati, T. Traffic (2000) [Pubmed]
  34. Identification of a plasma membrane-associated guanine nucleotide exchange factor for ARF6 in chromaffin cells. Possible role in the regulated exocytotic pathway. Caumont, A.S., Vitale, N., Gensse, M., Galas, M.C., Casanova, J.E., Bader, M.F. J. Biol. Chem. (2000) [Pubmed]
  35. The value of the QRS scoring system in assessing regional and global left ventricular ejection fraction early after myocardial infarction. Bergovec, M., Prpìć, H., Mihatov, S., Zigman, M., Vukosavić, D., Birtić, K., Franceschi, D., Barić, L. Eur. Heart J. (1993) [Pubmed]
  36. Effect of photoreceptor degeneration on RNA splicing and expression of AMPA receptors. Namekata, K., Okumura, A., Harada, C., Nakamura, K., Yoshida, H., Harada, T. Mol. Vis. (2006) [Pubmed]
WikiGenes - Universities