Phosphatase Subfamily PRL

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Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily PRL (PTP4A)


PRL is present in animals, and most basal eukaryotes, but is absent from fungi and plants (unpublished data from gOrtholog).


PRL has a CC1 fold phosphatase domain followed by a polybasic motif and a consensus prenylation motif.


PRL is short for Phosphatases of Regenerating Liver. There are three PRLs in human, PRL1, PRL2, PRL3 (PTP4A1-3), all of which have been identified as key contributors to metastasis in several human cancers [1, 2]. The molecular mechanisms of PRL phosphatases has been reviewed [3] in 2012.

PRL3 is implicated in cancer. For instance, deletion of PRL3 reduces clonogenicity and tumor-initiation ability of colitis-associated cancer cells in mice [4]. PRL3 (PTP4A3) independently predicts metastasis and survival in upper tract urothelial carcinoma treated with radical nephroureterectomy [5].

PTP4A3 has a number of reported protein substrates including ezrin [6] and p130cas [7]. All three human genes have activity against tyrosine-phosphorylated peptides [8].


  1. Hardy S, Uetani N, Wong N, Kostantin E, Labbé DP, Bégin LR, Mes-Masson A, Miranda-Saavedra D, and Tremblay ML. The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis. Oncogene. 2015 Feb 19;34(8):986-95. DOI:10.1038/onc.2014.33 | PubMed ID:24632616 | HubMed [tremblay14]
  2. Stephens BJ, Han H, Gokhale V, and Von Hoff DD. PRL phosphatases as potential molecular targets in cancer. Mol Cancer Ther. 2005 Nov;4(11):1653-61. DOI:10.1158/1535-7163.MCT-05-0248 | PubMed ID:16275986 | HubMed [Von-Hoff06]
  3. Rios P, Li X, and Köhn M. Molecular mechanisms of the PRL phosphatases. FEBS J. 2013 Jan;280(2):505-24. DOI:10.1111/j.1742-4658.2012.08565.x | PubMed ID:22413991 | HubMed [kohn12]
  4. Cramer JM, Zimmerman MW, Thompson T, Homanics GE, Lazo JS, and Lagasse E. Deletion of Ptp4a3 reduces clonogenicity and tumor-initiation ability of colitis-associated cancer cells in mice. Stem Cell Res. 2014 Jul;13(1):164-171. DOI:10.1016/j.scr.2014.05.004 | PubMed ID:24950307 | HubMed [Cramer15]
  5. Yeh HC, Li CC, Huang CN, Hour TC, Yeh BW, Li WM, Liang PI, Chang LL, Li CF, and Wu WJ. PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy. J Urol. 2015 Nov;194(5):1449-55. DOI:10.1016/j.juro.2015.05.101 | PubMed ID:26070892 | HubMed [Yeh15]
  6. Forte E, Orsatti L, Talamo F, Barbato G, De Francesco R, and Tomei L. Ezrin is a specific and direct target of protein tyrosine phosphatase PRL-3. Biochim Biophys Acta. 2008 Feb;1783(2):334-44. DOI:10.1016/j.bbamcr.2007.11.004 | PubMed ID:18078820 | HubMed [Forte]
  7. Matter WF, Estridge T, Zhang C, Belagaje R, Stancato L, Dixon J, Johnson B, Bloem L, Pickard T, Donaghue M, Acton S, Jeyaseelan R, Kadambi V, and Vlahos CJ. Role of PRL-3, a human muscle-specific tyrosine phosphatase, in angiotensin-II signaling. Biochem Biophys Res Commun. 2001 May 25;283(5):1061-8. DOI:10.1006/bbrc.2001.4881 | PubMed ID:11355880 | HubMed [Matter]
  8. Pathak MK, Dhawan D, Lindner DJ, Borden EC, Farver C, and Yi T. Pentamidine is an inhibitor of PRL phosphatases with anticancer activity. Mol Cancer Ther. 2002 Dec;1(14):1255-64. PubMed ID:12516958 | HubMed [Pathak]
All Medline abstracts: PubMed | HubMed