PREX2

Summary

Gene Symbol: PREX2
Description: phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2
Alias: DEP.2, DEPDC2, P-REX2, PPP1R129, phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein, DEP domain-containing protein 2, PtdIns(3,4,5)-dependent Rac exchanger 2, protein phosphatase 1, regulatory subunit 129
Species: human
Products:     PREX2

Top Publications

  1. Fine B, Hodakoski C, Koujak S, Su T, Saal L, 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 pubmed publisher
    ..Depletion of P-REX2a reduced amounts of phosphorylated AKT and growth in human cell lines with intact PTEN. Thus, P-REX2a is a component of the PI3K pathway that can antagonize PTEN in cancer cells. ..
  2. Yang M, Yen C, Chen Y, Fang C, Li C, Lee K, et al. Somatic mutations of PREX2 gene in patients with hepatocellular carcinoma. Sci Rep. 2019;9:2552 pubmed publisher
    ..The overexpression of Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2 (PREX2) is observed in various tumors, including HCC; and the frequent PREX2 mutations in melanoma are associated with ..
  3. Hodakoski C, Fine B, Hopkins B, Parsons R. Analysis of intracellular PTEN signaling and secretion. Methods. 2015;77-78:164-71 pubmed publisher
    ..Here, we review the methods used to identify and validate the existence of both PTEN-L and the P-REX2-PTEN complex, to determine their effects on PTEN phosphatase activity, and to examine their role in cellular physiology. ..
  4. Chroscinski D, Sampey D, Hewitt A. Registered report: Melanoma genome sequencing reveals frequent PREX2 mutations. elife. 2014;3: pubmed publisher
    ..describes the proposed replication plan of key experiments from "Melanoma genome sequencing reveals frequent PREX2 mutations" by Berger and colleagues, published in Nature in 2012 (Berger et al., 2012)...
  5. Jung S, Kim S, An C, Lee S, Jung E, Park H, et al. Clonal Structures of Regionally Synchronous Gastric Adenomas and Carcinomas. Clin Cancer Res. 2018;24:4715-4725 pubmed publisher
    ..In addition, we discovered novel KDM6A, PREX2, FAT1, KMT2C, GLI3, and RPL22 mutations and hypermutation in GAs, but did not identify recurrent ..
  6. Welch H. Regulation and function of P-Rex family Rac-GEFs. Small Gtpases. 2015;6:49-70 pubmed publisher
    ..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. ..
  7. Abiko H, Fujiwara S, Ohashi K, Hiatari R, Mashiko T, Sakamoto N, et al. Rho guanine nucleotide exchange factors involved in cyclic-stretch-induced reorientation of vascular endothelial cells. J Cell Sci. 2015;128:1683-95 pubmed publisher
    ..These results suggest that Solo is involved in cell-cell-adhesion-mediated mechanical signal transduction during cyclic-stretch-induced endothelial cell reorientation. ..
  8. Waddell N, Pajic M, Patch A, Chang D, Kassahn K, Bailey P, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518:495-501 pubmed publisher
    ..cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2)...
  9. Hernández García R, Iruela Arispe M, Reyes Cruz G, Vázquez Prado J. Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells. Vascul Pharmacol. 2015;74:60-72 pubmed publisher
    ..Expression of RASGRF2 and PREX2 increased significantly in response to VEGF, but most other RhoGEFs were unaffected...

More Information

Publications36

  1. Tong D, Zhao L, He K, Sun H, Cai D, Ni L, et al. MECP2 promotes the growth of gastric cancer cells by suppressing miR-338-mediated antiproliferative effect. Oncotarget. 2016;7:34845-59 pubmed publisher
    ..Altogether, our results indicate that MECP2 promote the proliferation of GC cells via miR-338 (miR-338-3p and miR-338-5p)-mediated antitumor and gene regulatory effect. ..
  2. Lucato C, Halls M, Ooms L, Liu H, Mitchell C, Whisstock J, et al. The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells. J Biol Chem. 2015;290:20827-40 pubmed publisher
  3. de Unamuno Bustos B, Murria Estal R, Pérez Simó G, de Juan Jiménez I, Escutia Muñoz B, Rodriguez Serna M, et al. Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel. Sci Rep. 2017;7:495 pubmed publisher
    ..The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100)...
  4. Multani S, Pradhan S, Saranath D. Gene polymorphisms and oral cancer risk in tobacco habitués. Tumour Biol. 2016;37:6169-76 pubmed publisher
    ..The SNPs rs2124437 (RASGRP3), rs1335022 (GRIK2), rs4512367 (PREX2), rs4748011 (CCDC3), and rs1435218 (LNX1) were analyzed in 500 histopathologically confirmed oral cancers and 500 ..
  5. Hodakoski C, Hopkins B, Barrows D, Mense S, Keniry M, Anderson K, et al. Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis. Proc Natl Acad Sci U S A. 2014;111:155-60 pubmed publisher
    ..Consistent with its function as a PTEN inhibitor, deletion of Prex2 in fibroblasts and mice results in increased Pten activity and decreased insulin signaling in liver and adipose ..
  6. Barrows D, Schoenfeld S, Hodakoski C, Silkov A, Honig B, Couvillon A, et al. p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. J Biol Chem. 2015;290:28915-31 pubmed publisher
    Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 2 (PREX2) is a guanine nucleotide exchange factor (GEF) for the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase, facilitating the exchange of GDP for GTP on ..
  7. Leslie N. P-REX2a driving tumorigenesis by PTEN inhibition. Sci Signal. 2009;2:pe68 pubmed publisher
    ..This suggests that aberrant control of PTEN by P-REX2a may represent a key tumorigenic mechanism, in agreement with recent studies supporting the pathological relevance of several other proposed PTEN regulators. ..
  8. Barrio Real L, Kazanietz M. Rho GEFs and cancer: linking gene expression and metastatic dissemination. Sci Signal. 2012;5:pe43 pubmed publisher
  9. Berger M, Hodis E, Heffernan T, Deribe Y, Lawrence M, Protopopov A, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature. 2012;485:502-6 pubmed publisher
    ..Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and ..
  10. Hernández Negrete I, Carretero Ortega J, Rosenfeldt H, Hernández García R, Calderón Salinas J, 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 pubmed
    ..mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration. ..
  11. Liu L, Liu Z, Wang H, Chen L, Ruan F, Zhang J, et al. Knockdown of PREX2a inhibits the malignant phenotype of glioma cells. Mol Med Rep. 2016;13:2301-7 pubmed publisher
  12. Davis R. Melanoma mystery. elife. 2017;6: pubmed publisher
    Biological variability has confounded efforts to confirm the role of PREX2 mutations in melanoma.
  13. Lissanu Deribe Y. Interplay between PREX2 mutations and the PI3K pathway and its effect on epigenetic regulation of gene expression in NRAS-mutant melanoma. Small Gtpases. 2016;7:178-85 pubmed publisher
    b>PREX2 is a PTEN interacting protein that is significantly mutated in melanoma and pancreatic ductal adenocarcinoma. Recently, we reported the mechanistic basis of melanomagenesis by PREX2 mutations...
  14. Lan X, Xiao F, Ding Q, Liu J, Liu J, Li J, et al. The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2. J Mol Histol. 2014;45:689-96 pubmed publisher
    ..G protein-coupled receptors (GPCR) activated by CXCL9, Phosphatidylinositol-3, 4, 5-trisphosphate RAC Exchanger 2 (PREX2) mRNA expression of the liver cancer cell lines was elevated after co-cultured with rhCXCL9...
  15. 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 pubmed
    ..Together, they form an enzyme family capable of mediating Rac signalling downstream of G protein-coupled receptors and phosphoinositide 3-kinase. ..
  16. Barrows D, He J, Parsons R. PREX1 Protein Function Is Negatively Regulated Downstream of Receptor Tyrosine Kinase Activation by p21-activated Kinases (PAKs). J Biol Chem. 2016;291:20042-54 pubmed publisher
    ..PREX1 and PREX2 GEF activity is activated by the second messengers PIP3 and G??, and further regulation of PREX GEF activity ..
  17. Joseph R, Norris F. 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 pubmed
    ..Thus substrate recognition can now be added to the growing list of functions that are being attributed to the PH domain of Dbl family GEFs. ..
  18. Chen X, Pan M, Han L, Lu H, Hao X, Dong Q. miR-338-3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a. FEBS Lett. 2013;587:3729-37 pubmed publisher
    ..Overall, this study demonstrates that miR-338-3p affects the PTEN/Akt pathway by down-regulating PREX2a. This newly identified function of miR-338-3p provides novel insights into neuroblastoma and may foster therapeutic applications. ..
  19. Mense S, Barrows D, Hodakoski C, Steinbach N, Schoenfeld D, Su W, et al. PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion. Sci Signal. 2015;8:ra32 pubmed publisher
    ..b>PREX2, a widely distributed GEF that activates the GTPase RAC1, binds to and inhibits PTEN...
  20. Lissanu Deribe Y, Shi Y, Rai K, Nezi L, Amin S, Wu C, et al. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma. Proc Natl Acad Sci U S A. 2016;113:E1296-305 pubmed publisher
    b>PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal ..
  21. Li C, Yen C, Chen Y, Lee K, Fang C, Zhang X, et al. Characterization of the GNMT-HectH9-PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma. Int J Cancer. 2017;140:2284-2297 pubmed publisher
    ..We identified PREX2, a novel PTEN inhibitor, as a GNMT-interacting protein...
  22. Horrigan S, Courville P, Sampey D, Zhou F, Cai S. Replication Study: Melanoma genome sequencing reveals frequent PREX2 mutations. elife. 2017;6: pubmed publisher
    ..how we intended to replicate selected experiments from the paper "Melanoma genome sequencing reveals frequent PREX2 mutations" (Berger et al., 2012). Here we report the results of those experiments...
  23. Dai Z, Xie J, Lei P, Hu Y. Knockdown of PREX2a inhibits the malignant phenotype of osteosarcoma cells. Mol Med Rep. 2016;13:1930-6 pubmed publisher
    ..The results of the present study suggested that PREX2a may act as an oncogene in OS via the inhibition of PTEN activity and activation of PI3K signaling. ..
  24. Liu J, Cao L, Feng Y, Li Y, Li T. MiR-338-3p inhibits TNF-α-induced lipogenesis in human sebocytes. Biotechnol Lett. 2017;39:1343-1349 pubmed publisher
    ..PREX2a overexpression consistently restored lipogenesis and AKT phosphorylation attenuated by miR-338-3p. MiR-338-3p suppresses the TNF-α-induced lipogenesis in sebocytes by targeting PREX2a and down-regulating PI3K/AKT signaling. ..
  25. Srijakotre N, Man J, Ooms L, Lucato C, Ellisdon A, Mitchell C. P-Rex1 and P-Rex2 RacGEFs and cancer. Biochem Soc Trans. 2017;45:963-77 pubmed publisher
    ..Emerging clinical data predict that changes in expression or mutation of P-Rex1 and P-Rex2 may lead to changes in tumour outcome, particularly in breast cancer and melanoma. ..
  26. Rosenfeldt H, Vazquez Prado J, Gutkind J. P-REX2, a novel PI-3-kinase sensitive Rac exchange factor. FEBS Lett. 2004;572:167-71 pubmed
    ..P-REX2 promoted increased levels of GTP-bound Rac that could be further stimulated by enhancing PI-3K activity. Thus, P-REX2 may serve as a novel link between Rac activation and the PI-3 kinase pathway. ..
  27. Guo B, Liu L, Yao J, Ma R, Chang D, Li Z, et al. miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a. Mol Cancer Res. 2014;12:313-21 pubmed publisher
    ..Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of ..