Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Katherine FigellaEmail author
  • Brad Allen Bryan
  • Mingyao Liu
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_337


Historical Background

The gene for ARHGEF25 is located on human chromosome 12q13.3, and its expression encodes a Rho-family guanine nucleotide exchange factor (GEF) protein composed of a Dbl homology domain and a pleckstrin homology domain flanked by short N- and C-termini (Souchet et al. 2002; Guo et al. 2003). ARHGEF25 belongs to a family composed of over 60 known human GEFs. This family of proteins serves as enzymes which catalyze the activation of the Rho family of small GTPases through stimulating the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on Rho proteins, thus modulating a broad range of cellular processes in eukaryotic cells such as cell proliferation, gene expression, and actin cytoskeletal organization (Hall and Nobes 2000). Two known alternative splice variants of the ARHGEF25 gene have been identified (GEFT and p63RhoGEF) (Fig. 1), and these protein products share high...
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  1. Bryan B, Kumar V, Stafford LJ, Cai Y, Wu G, Liu M. GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation. J Biol Chem. 2004;279(44):45824–32.PubMedCrossRefGoogle Scholar
  2. Bryan BA, Mitchell DC, Zhao L, Ma W, Stafford LJ, Teng BB, et al. Modulation of muscle regeneration, myogenesis, and adipogenesis by the Rho family guanine nucleotide exchange factor GEFT. Mol Cell Biol. 2005;25(24):11089–101.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bryan BA, Cai Y, Liu M. The Rho-family guanine nucleotide exchange factor GEFT enhances retinoic acid- and cAMP-induced neurite outgrowth. J Neurosci Res. 2006;83(7):1151–9.PubMedCrossRefGoogle Scholar
  4. Guo X, Stafford LJ, Bryan B, Xia C, Ma W, Wu X, et al. A Rac/Cdc42-specific exchange factor, GEFT, induces cell proliferation, transformation, and migration. J Biol Chem. 2003;278(15):13207–15.PubMedCrossRefGoogle Scholar
  5. Hall A, Nobes CD. Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Philos Trans R Soc Lond B Biol Sci. 2000;355(1399):965–70.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Komai K, Okayama R, Kitagawa M, Yagi H, Chihara K, Shiozawa S. Alternative splicing variants of the human DBL (MCF-2) proto-oncogene. Biochem Biophys Res Commun. 2002;299(3):455–8.PubMedCrossRefGoogle Scholar
  7. Liu D, Yang X, Yang D, Songyang Z. Genetic screens in mammalian cells by enhanced retroviral mutagens. Oncogene. 2000;19(52):5964–72.PubMedCrossRefGoogle Scholar
  8. Lutz S, Freichel-Blomquist A, Yang Y, Rümenapp U, Jakobs KH, Schmidt M, et al. The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem. 2005;280(12):11134–9.PubMedCrossRefGoogle Scholar
  9. Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance MR, Vettel C, et al. Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science. 2007;318(5858):1923–7.PubMedCrossRefGoogle Scholar
  10. Mitchell DC, Bryan BA, Liu JP, Liu WB, Zhang L, Qu J, et al. Developmental expression of three small GTPases in the mouse eye. Mol Vis. 2007;13:1144–53.PubMedPubMedCentralGoogle Scholar
  11. Mitchell DC, Bryan BA, Liu L, XH H, Huang XQ, Ji WK, et al. GEFT, A Rho family guanine nucleotide exchange factor, regulates lens differentiation through a Rac1-mediated mechanism. Curr Mol Med. 2011;11(6):465–80.PubMedCrossRefGoogle Scholar
  12. Rojas RJ, Yohe ME, Gershburg S, Kawano T, Kozasa T, Sondek J. Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain. J Biol Chem. 2007;282:29201–10.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Shankaranarayanan A, Thal DM, Tesmer VM, Roman DL, Neubig RR, Kozasa T, Tesmer JJ. Assembly of high order G alpha q-effector complexes with RGS proteins. J Biol Chem. 2008;283(50):34923–34.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Shankaranarayanan A, Boguth CA, Lutz S, Vettel C, Uhlemann F, Aittaleb M, et al. Galpha q allosterically activates and relieves autoinhibition of p63RhoGEF. Cell Signal. 2010;22(7):1114–23.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Smith TK, Hager HA, Francis R, Kilkenny DM, Lo CW, Bader DM. Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity. Proc Natl Acad Sci USA. 2008;105(24):8298–303.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Souchet M, Portales-Casamar E, Mazurais D, Schmidt S, Léger I, Javré JL, et al. Human p63RhoGEF, a novel RhoA-specific guanine nucleotide exchange factor, is localized in cardiac sarcomere. J Cell Sci. 2002;115(Pt3):629–40.PubMedPubMedCentralGoogle Scholar
  17. Swenson-Fields KI, Sandquist JC, Rossol-Allison J, Blat IC, Wennerberg K, Burridge K, et al. MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF. Mol Cell. 2008;32(1):43–56.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Wuertz CM, Lorincz A, Vettel C, Thomas MA, Wieland T, Lutz S. p63RhoGEF–a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells. FASEB J. 2010;24(12):4865–76.PubMedCrossRefGoogle Scholar
  19. Yeung WW, Wong YH. The RhoA-specific guanine nucleotide exchange factor p63RhoGEF binds to activated Galpha(16) and inhibits the canonical phospholipase Cbeta pathway. Cell Signal. 2009;21(8):1317–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Katherine Figella
    • 1
    Email author
  • Brad Allen Bryan
    • 1
    • 2
  • Mingyao Liu
    • 3
    • 4
  1. 1.Department of Biology, Ghosh Science and Technology CenterWorcester State UniversityWorcesterUSA
  2. 2.Center of Excellence in Cancer Research, Department of Biomedical SciencesTexas Tech University Health Sciences CenterEl PasoUSA
  3. 3.Mingyao Liu Lab Department of Molecular and Cellular MedicineInstitute of Biosciences and Technology, Texas A&M University Health Science CenterHoustonUSA
  4. 4.Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences, School of Life Sciences, East China Normal UniversityShanghaiChina