The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins.[4]
Clinical significance
The protein has been implicated in the spread of melanoma skin cancer.[5]
References
↑Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, Tempst P, Hawkins PT, Stephens LR (Apr 2002). "P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac". Cell. 108 (6): 809–21. doi:10.1016/S0092-8674(02)00663-3. PMID11955434.
↑Hill K, Krugmann S, Andrews SR, Coadwell WJ, Finan P, Welch HC, Hawkins PT, Stephens LR (Feb 2005). "Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits". J Biol Chem. 280 (6): 4166–73. doi:10.1074/jbc.M411262200. PMID15545267.
↑Mayeenuddin LH, Garrison JC (Jan 2006). "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. 281 (4): 1921–8. doi:10.1074/jbc.M506035200. PMID16301320.
Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID12168954.
Nagase T, Kikuno R, Ishikawa KI, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID10718198.
Fossey SC, Mychaleckyj JC, Pendleton JK, et al. (2001). "A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20". Genomics. 76 (1–3): 45–57. doi:10.1006/geno.2001.6584. PMID11549316.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID11780052.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Zhao T, Nalbant P, Hoshino M, et al. (2007). "Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function". J. Leukoc. Biol. 81 (4): 1127–36. doi:10.1189/jlb.0406251. PMID17227822.
Hernández-Negrete I, Carretero-Ortega J, Rosenfeldt H, et al. (2007). "P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration". J. Biol. Chem. 282 (32): 23708–15. doi:10.1074/jbc.M703771200. PMID17565979.
Barber MA, Donald S, Thelen S, et al. (2007). "Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase". J. Biol. Chem. 282 (41): 29967–76. doi:10.1074/jbc.M701877200. PMID17698854.