| Structural highlights
Function
PTPRJ_HUMAN Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, RET (variant MEN2A), KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2. Plays a role in cell adhesion, migration, proliferation and differentiation. Involved in vascular development. Regulator of macrophage adhesion and spreading. Positively affects cell-matrix adhesion. Positive regulator of platelet activation and thrombosis. Negative regulator of cell proliferation. Negative regulator of PDGF-stimulated cell migration; through dephosphorylation of PDGFR. Positive regulator of endothelial cell survival, as well as of VEGF-induced SRC and AKT activation; through KDR dephosphorylation. Negative regulator of EGFR signaling pathway; through EGFR dephosphorylation. Enhances the barrier function of epithelial junctions during reassembly. Negatively regulates T-cell receptor (TCR) signaling. Upon T-cell TCR activation, it is up-regulated and excluded from the immunological synapses, while upon T-cell-antigen presenting cells (APC) disengagement, it is no longer excluded and can dephosphorylate PLCG1 and LAT to down-regulate prolongation of signaling.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Protein tyrosine phosphatases (PTPs) play a critical role in regulating cellular functions by selectively dephosphorylating their substrates. Here we present 22 human PTP crystal structures that, together with prior structural knowledge, enable a comprehensive analysis of the classical PTP family. Despite their largely conserved fold, surface properties of PTPs are strikingly diverse. A potential secondary substrate-binding pocket is frequently found in phosphatases, and this has implications for both substrate recognition and development of selective inhibitors. Structural comparison identified four diverse catalytic loop (WPD) conformations and suggested a mechanism for loop closure. Enzymatic assays revealed vast differences in PTP catalytic activity and identified PTPD1, PTPD2, and HDPTP as catalytically inert protein phosphatases. We propose a "head-to-toe" dimerization model for RPTPgamma/zeta that is distinct from the "inhibitory wedge" model and that provides a molecular basis for inhibitory regulation. This phosphatome resource gives an expanded insight into intrafamily PTP diversity, catalytic activity, substrate recognition, and autoregulatory self-association.
Large-scale structural analysis of the classical human protein tyrosine phosphatome.,Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S Cell. 2009 Jan 23;136(2):352-63. PMID:19167335[20]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ de la Fuente-Garcia MA, Nicolas JM, Freed JH, Palou E, Thomas AP, Vilella R, Vives J, Gaya A. CD148 is a membrane protein tyrosine phosphatase present in all hematopoietic lineages and is involved in signal transduction on lymphocytes. Blood. 1998 Apr 15;91(8):2800-9. PMID:9531590
- ↑ Tangye SG, Wu J, Aversa G, de Vries JE, Lanier LL, Phillips JH. Negative regulation of human T cell activation by the receptor-type protein tyrosine phosphatase CD148. J Immunol. 1998 Oct 15;161(8):3803-7. PMID:9780142
- ↑ Kovalenko M, Denner K, Sandstrom J, Persson C, Gross S, Jandt E, Vilella R, Bohmer F, Ostman A. Site-selective dephosphorylation of the platelet-derived growth factor beta-receptor by the receptor-like protein-tyrosine phosphatase DEP-1. J Biol Chem. 2000 May 26;275(21):16219-26. PMID:10821867
- ↑ Baker JE, Majeti R, Tangye SG, Weiss A. Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation. Mol Cell Biol. 2001 Apr;21(7):2393-403. PMID:11259588 doi:http://dx.doi.org/10.1128/MCB.21.7.2393-2403.2001
- ↑ Persson C, Engstrom U, Mowbray SL, Ostman A. Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1. FEBS Lett. 2002 Apr 24;517(1-3):27-31. PMID:12062403
- ↑ Holsinger LJ, Ward K, Duffield B, Zachwieja J, Jallal B. The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120(ctn). Oncogene. 2002 Oct 10;21(46):7067-76. PMID:12370829 doi:http://dx.doi.org/10.1038/sj.onc.1205858
- ↑ Palka HL, Park M, Tonks NK. Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1. J Biol Chem. 2003 Feb 21;278(8):5728-35. Epub 2002 Dec 9. PMID:12475979 doi:http://dx.doi.org/10.1074/jbc.M210656200
- ↑ Lin J, Weiss A. The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling. J Cell Biol. 2003 Aug 18;162(4):673-82. Epub 2003 Aug 11. PMID:12913111 doi:http://dx.doi.org/10.1083/jcb.200303040
- ↑ Kellie S, Craggs G, Bird IN, Jones GE. The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation. J Cell Sci. 2004 Feb 1;117(Pt 4):609-18. Epub 2004 Jan 6. PMID:14709717 doi:http://dx.doi.org/10.1242/jcs.00879
- ↑ Iervolino A, Iuliano R, Trapasso F, Viglietto G, Melillo RM, Carlomagno F, Santoro M, Fusco A. The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins. Cancer Res. 2006 Jun 15;66(12):6280-7. PMID:16778204 doi:http://dx.doi.org/10.1158/0008-5472.CAN-06-0228
- ↑ Balavenkatraman KK, Jandt E, Friedrich K, Kautenburger T, Pool-Zobel BL, Ostman A, Bohmer FD. DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients. Oncogene. 2006 Oct 12;25(47):6319-24. Epub 2006 May 8. PMID:16682945 doi:http://dx.doi.org/10.1038/sj.onc.1209647
- ↑ Tsuboi N, Utsunomiya T, Roberts RL, Ito H, Takahashi K, Noda M, Takahashi T. The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. Biochem J. 2008 Jul 1;413(1):193-200. doi: 10.1042/BJ20071317. PMID:18348712 doi:http://dx.doi.org/10.1042/BJ20071317
- ↑ Tarcic G, Boguslavsky SK, Wakim J, Kiuchi T, Liu A, Reinitz F, Nathanson D, Takahashi T, Mischel PS, Ng T, Yarden Y. An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis. Curr Biol. 2009 Nov 17;19(21):1788-98. doi: 10.1016/j.cub.2009.09.048. PMID:19836242 doi:http://dx.doi.org/10.1016/j.cub.2009.09.048
- ↑ Sallee JL, Burridge K. Density-enhanced phosphatase 1 regulates phosphorylation of tight junction proteins and enhances barrier function of epithelial cells. J Biol Chem. 2009 May 29;284(22):14997-5006. doi: 10.1074/jbc.M901901200. Epub, 2009 Mar 30. PMID:19332538 doi:http://dx.doi.org/10.1074/jbc.M901901200
- ↑ Sacco F, Tinti M, Palma A, Ferrari E, Nardozza AP, Hooft van Huijsduijnen R, Takahashi T, Castagnoli L, Cesareni G. Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases. J Biol Chem. 2009 Aug 14;284(33):22048-58. doi: 10.1074/jbc.M109.002758. Epub, 2009 Jun 3. PMID:19494114 doi:http://dx.doi.org/10.1074/jbc.M109.002758
- ↑ Chabot C, Spring K, Gratton JP, Elchebly M, Royal I. New role for the protein tyrosine phosphatase DEP-1 in Akt activation and endothelial cell survival. Mol Cell Biol. 2009 Jan;29(1):241-53. doi: 10.1128/MCB.01374-08. Epub 2008 Oct, 20. PMID:18936167 doi:http://dx.doi.org/10.1128/MCB.01374-08
- ↑ Petermann A, Haase D, Wetzel A, Balavenkatraman KK, Tenev T, Guhrs KH, Friedrich S, Nakamura M, Mawrin C, Bohmer FD. Loss of the protein-tyrosine phosphatase DEP-1/PTPRJ drives meningioma cell motility. Brain Pathol. 2011 Jul;21(4):405-18. doi: 10.1111/j.1750-3639.2010.00464.x. Epub , 2010 Dec 27. PMID:21091576 doi:http://dx.doi.org/10.1111/j.1750-3639.2010.00464.x
- ↑ Omerovic J, Clague MJ, Prior IA. Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras-mutated cancer cells. Biochem J. 2010 Jan 27;426(1):65-72. doi: 10.1042/BJ20091413. PMID:19922411 doi:http://dx.doi.org/10.1042/BJ20091413
- ↑ Arora D, Stopp S, Bohmer SA, Schons J, Godfrey R, Masson K, Razumovskaya E, Ronnstrand L, Tanzer S, Bauer R, Bohmer FD, Muller JP. Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling. J Biol Chem. 2011 Apr 1;286(13):10918-29. doi: 10.1074/jbc.M110.205021. Epub 2011, Jan 24. PMID:21262971 doi:10.1074/jbc.M110.205021
- ↑ Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. PMID:19167335 doi:http://dx.doi.org/10.1016/j.cell.2008.11.038
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