Regulation and function of P-Rex family Rac-GEFs

Small GTPases. 2015;6(2):49-70. doi: 10.4161/21541248.2014.973770. Epub 2015 May 11.

Abstract

The P-Rex family are Dbl-type guanine-nucleotide exchange factors for Rac family small G proteins. They are distinguished from other Rac-GEFs through their synergistic mode of activation by the lipid second messenger phosphatidyl inositol (3,4,5) trisphosphate and the Gβγ subunits of heterotrimeric G proteins, thus acting as coincidence detectors for phosphoinositide 3-kinase and G protein coupled receptor signaling. Work in genetically-modified mice has shown that P-Rex1 has physiological importance in the inflammatory response and the migration of melanoblasts during development, whereas P-Rex2 controls the dendrite morphology of cerebellar Purkinje neurons as well as glucose homeostasis in liver and adipose tissue. Deregulation of P-Rex1 and P-Rex2 expression occurs in many types of cancer, and P-Rex2 is frequently mutated in melanoma. Both GEFs promote tumor growth or metastasis. This review critically evaluates the P-Rex literature and tools available and highlights exciting recent developments and open questions.

Keywords: GEFs; P-Rex1; P-Rex2; P-Rex2b; PREX1; PREX2; PREX2A; Rac; Rho family; aa, amino acid; BRET, bioluminescence resonance energy transfer; coIP, coimmunoprecipitation; EST, expressed sequence tag; GEF, guanine-nucleotide exchange factor; HDAC, histone deacetylase; iDHPH, isolated Dbl homology (DH) /pleckstrin homology (PH) doma; guanine-nucleotide exchange factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / metabolism*
  • Humans
  • Neoplasms / metabolism*
  • Protein Binding
  • Rho Guanine Nucleotide Exchange Factors / chemistry
  • Rho Guanine Nucleotide Exchange Factors / genetics
  • Rho Guanine Nucleotide Exchange Factors / metabolism*
  • Second Messenger Systems
  • rac GTP-Binding Proteins / chemistry
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Rho Guanine Nucleotide Exchange Factors
  • rac GTP-Binding Proteins