title: Regulation and function of P-Rex family Rac-GEFs.
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.
authors.affiliation: a Signalling Programme; Babraham Institute ; Cambridge , UK.
authors.forename: Heidi C E
authors.initials: HC
authors.lastname: Welch
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D064067:Rho Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D020744:rac GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D064067:Rho Guanine Nucleotide Exchange Factors; D020744:rac GTP-Binding Proteins
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