Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

P-Rex

  • Daisuke Urano
  • Hiroshi Itoh
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_182

Synonyms

Historical Background

A phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger (P-Rex) is an intracellular signaling molecule that regulates leukocyte function and neuronal development by activating a small guanine nucleotide-binding protein, Rac. The Homo sapiens genome encodes two P-Rex genes, P-Rex1 and P-Pex2. In 2002, Welch et al. purified a PIP3-dependent Rac activator from pig neutrophil lysates, identified a 196 kDa Dbl-like GEF (guanine nucleotide exchange factor) protein for Rac, and designated it as P-Rex1 (Welch et al. 2002). They characterized its synergistic activation by Gβγ subunits of heterotrimeric G proteins and PIP3, and its...

This is a preview of subscription content, log in to check access.

References

  1. Barber MA, Donald S, Thelen S, Anderson KE, Thelen M, Welch HC. Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase. J Biol Chem. 2007;282:29967–76.PubMedGoogle Scholar
  2. Donald S, Hill K, Lecureuil C, Barnouin R, Krugmann S, John Coadwell W, et al. P-Rex2, a new guanine-nucleotide exchange factor for Rac. FEBS Lett. 2004;572:172–6.PubMedGoogle Scholar
  3. Donald S, Humby T, Fyfe I, Segonds-Pichon A, Walker SA, Andrews SR, et al. P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination. Proc Natl Acad Sci USA. 2008;105:4483–8.PubMedGoogle Scholar
  4. Dong X, Mo Z, Bokoch G, Guo C, Li Z, Wu D. P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Curr Biol. 2005;15:1874–9.PubMedGoogle Scholar
  5. Fine B, Hodakoski C, Koujak S, Su T, Saal LH, Maurer M, et al. Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Science. 2009;325:1261–5.PubMedGoogle Scholar
  6. Hernandez-Negrete I, Carretero-Ortega J, Rosenfeldt H, Hernandez-Garcia R, Calderon-Salinas JV, Reyes-Cruz G, et al. P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. J Biol Chem. 2007;282:23708–15.PubMedGoogle Scholar
  7. Hill K, Krugmann S, Andrews SR, Coadwell WJ, Finan P, Welch HC, et al. Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits. J Biol Chem. 2005;280:4166–73.PubMedGoogle Scholar
  8. Joseph RE, Norris FA. Substrate specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor P-Rex2. J Biol Chem. 2005;280:27508–12.PubMedGoogle Scholar
  9. Kim EK, Yun SJ, Ha JM, Kim YW, Jin IH, Yun J, et al. Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis. Oncogene. 2011;30:2954–63.PubMedGoogle Scholar
  10. Lawson CD, Donald S, Anderson KE, Patton DT, Welch HC. P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses. J Immunol. 2011;186:1467–76.PubMedGoogle Scholar
  11. Mayeenuddin LH, Garrison JC. Phosphorylation of P-Rex1 by the cyclic AMP-dependent protein kinase inhibits the phosphatidylinositiol (3,4,5)-trisphosphate and Gbetagamma-mediated regulation of its activity. J Biol Chem. 2006;281:1921–8.PubMedGoogle Scholar
  12. Montero JC, Seoane S, Ocana A, Pandiella A. P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer. Oncogene. 2011;30:1059–71.PubMedGoogle Scholar
  13. Qin J, Xie Y, Wang B, Hoshino M, Wolff DW, Zhao J, et al. Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis. Oncogene. 2009;28:1853–63.PubMedGoogle Scholar
  14. Rosenfeldt H, Vazquez-Prado J, Gutkind JS. P-REX2, a novel PI-3-kinase sensitive Rac exchange factor. FEBS Lett. 2004;572:167–71.PubMedGoogle Scholar
  15. Sosa MS, Lopez-Haber C, Yang C, Wang H, Lemmon MA, Busillo JM, et al. Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Mol Cell. 2010;40:877–92.PubMedGoogle Scholar
  16. Urano D, Nakata A, Mizuno N, Tago K, Itoh H. Domain-domain interaction of P-Rex1 is essential for the activation and inhibition by G protein betagamma subunits and PKA. Cell Signal. 2008;20:1545–54.PubMedGoogle Scholar
  17. Wang Z, Dong X, Li Z, Smith JD, Wu D. Lack of a significant role of P-Rex1, a major regulator of macrophage Rac1 activation and chemotaxis, in atherogenesis. Prostaglandins Other Lipid Mediat. 2008;87:9–13.PubMedGoogle Scholar
  18. Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, et al. P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell. 2002;108:809–21.PubMedGoogle Scholar
  19. Welch HC, Condliffe AM, Milne LJ, Ferguson GJ, Hill K, Webb LM, et al. P-Rex1 regulates neutrophil function. Curr Biol. 2005;15:1867–73.PubMedGoogle Scholar
  20. Yoshizawa M, Kawauchi T, Sone M, Nishimura YV, Terao M, Chihama K, et al. Involvement of a Rac activator, P-Rex1, in neurotrophin-derived signaling and neuronal migration. J Neurosci. 2005;25:4406–19.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of BiologyUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Medical ScienceNara Institute of Science and TechnologyIkomaJapan