Phosphatase Subfamily PTPRB
Phosphatase Classification: Fold CC1: Superfamily CC1: Family PTP: Subfamily PTPRB
PTPRC (CD45) is a vertebrate-specific receptor PTP involved in immune signaling.
Evolution
PTPRB subfamily is found across metazoan. It has multiple copies per genomes in bilateral.
Domain Structure
Functions
(summary)
PTPRB (VE-PTP)
PTPRB, a.k.a. vascular endothelial protein tyrosine phosphatase (VE-PTP), is expressed specifically in endothelial cells and regulates the spreading and migration of endothelial cells during angiogenesis [1]. PTPRB binds to vascular E-cadherin (VE-cadherin) through an extracellular domain and reduces the tyrosine phosphorylation of VE-cadherin. But, the reduction of tyrosine phosphorylation seems independently of its enzymatic activity, since catalytically inactive mutant form of PTPRB had the same effect on VE-cadherin phosphorylation [2]. PTPRB associates with endothelial cell (EC)-selective receptor tyrosine kinase Tie2, which maintains vascular integrity [3, 4, 5, 6]. PTPRB regulates vascular endothelial growth factor receptor 2 activity thereby modulating the VEGF-response during angiogenesis [7].
PTPRB is intrinsically active and its inactivation is dependent on its ligand pleiotrophin (PTN) which is a platelet-derived growth factor-inducible, 18-kDa heparin-binding cytokine that signals diverse phenotypes in normal and deregulated cellular growth and differentiation [8]. PTPRB is glycosylated protein (phosphacan).
PTPRB mutations are observed in cancers. Its mutations are recurrent in angiosarcoma [9]. PTPRB mediates glial tumor cell adhesion by binding to tenascin C [10].
PTPRB interacts with neuronal receptors and promotes neurite outgrowth [11].
References
- Mori M, Murata Y, Kotani T, Kusakari S, Ohnishi H, Saito Y, Okazawa H, Ishizuka T, Mori M, and Matozaki T. Promotion of cell spreading and migration by vascular endothelial-protein tyrosine phosphatase (VE-PTP) in cooperation with integrins. J Cell Physiol. 2010 Jul;224(1):195-204. DOI:10.1002/jcp.22122 |
- Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, and Vestweber D. VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. EMBO J. 2002 Sep 16;21(18):4885-95. DOI:10.1093/emboj/cdf497 |
- Fachinger G, Deutsch U, and Risau W. Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2. Oncogene. 1999 Oct 21;18(43):5948-53. DOI:10.1038/sj.onc.1202992 |
- Winderlich M, Keller L, Cagna G, Broermann A, Kamenyeva O, Kiefer F, Deutsch U, Nottebaum AF, and Vestweber D. VE-PTP controls blood vessel development by balancing Tie-2 activity. J Cell Biol. 2009 May 18;185(4):657-71. DOI:10.1083/jcb.200811159 |
- Yacyshyn OK, Lai PF, Forse K, Teichert-Kuliszewska K, Jurasz P, and Stewart DJ. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis. 2009;12(1):25-33. DOI:10.1007/s10456-008-9126-0 |
- Shen J, Frye M, Lee BL, Reinardy JL, McClung JM, Ding K, Kojima M, Xia H, Seidel C, Lima e Silva R, Dong A, Hackett SF, Wang J, Howard BW, Vestweber D, Kontos CD, Peters KG, and Campochiaro PA. Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature. J Clin Invest. 2014 Oct;124(10):4564-76. DOI:10.1172/JCI74527 |
- Mellberg S, Dimberg A, Bahram F, Hayashi M, Rennel E, Ameur A, Westholm JO, Larsson E, Lindahl P, Cross MJ, and Claesson-Welsh L. Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis. FASEB J. 2009 May;23(5):1490-502. DOI:10.1096/fj.08-123810 |
- Meng K, Rodriguez-Peña A, Dimitrov T, Chen W, Yamin M, Noda M, and Deuel TF. Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2603-8. DOI:10.1073/pnas.020487997 |
- Behjati S, Tarpey PS, Sheldon H, Martincorena I, Van Loo P, Gundem G, Wedge DC, Ramakrishna M, Cooke SL, Pillay N, Vollan HKM, Papaemmanuil E, Koss H, Bunney TD, Hardy C, Joseph OR, Martin S, Mudie L, Butler A, Teague JW, Patil M, Steers G, Cao Y, Gumbs C, Ingram D, Lazar AJ, Little L, Mahadeshwar H, Protopopov A, Al Sannaa GA, Seth S, Song X, Tang J, Zhang J, Ravi V, Torres KE, Khatri B, Halai D, Roxanis I, Baumhoer D, Tirabosco R, Amary MF, Boshoff C, McDermott U, Katan M, Stratton MR, Futreal PA, Flanagan AM, Harris A, and Campbell PJ. Recurrent PTPRB and PLCG1 mutations in angiosarcoma. Nat Genet. 2014 Apr;46(4):376-379. DOI:10.1038/ng.2921 |
- Adamsky K, Schilling J, Garwood J, Faissner A, and Peles E. Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor protein tyrosine phosphatase beta (RPTPbeta) to tenascin C. Oncogene. 2001 Feb 1;20(5):609-18. DOI:10.1038/sj.onc.1204119 |
- Garwood J, Heck N, Reichardt F, and Faissner A. Phosphacan short isoform, a novel non-proteoglycan variant of phosphacan/receptor protein tyrosine phosphatase-beta, interacts with neuronal receptors and promotes neurite outgrowth. J Biol Chem. 2003 Jun 27;278(26):24164-73. DOI:10.1074/jbc.M211721200 |