| PTPRB | 
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| | Available structures | 
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 | PDB | Ortholog search: PDBe RCSB | 
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 | | List of PDB id codes | 
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 | 2AHS, 2H02, 2H03, 2H04, 2HC1, 2HC2, 2I3R, 2I3U, 2I4E, 2I4G, 2I4H, 2I5X | 
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| Identifiers | 
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| Aliases | PTPRB, HPTP-BETA, HPTPB, PTPB, R-PTP-BETA, VEPTP, protein tyrosine phosphatase, receptor type B, protein tyrosine phosphatase receptor type B | 
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| External IDs | OMIM: 176882; MGI: 97809; HomoloGene: 2125; GeneCards: PTPRB; OMA:PTPRB - orthologs | 
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| | RNA expression pattern | 
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 | Bgee | | Human | Mouse (ortholog) | 
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 | | Top expressed in |  | endothelial cell
 lower lobe of lung
 visceral pleura
 right lung
 right ventricle
 parietal pleura
 upper lobe of lung
 upper lobe of left lung
 epithelium of colon
 Skeletal muscle tissue of biceps brachii
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 | | Top expressed in |  | right lung
 right lung lobe
 left lung
 external carotid artery
 internal carotid artery
 carotid body
 left lung lobe
 digastric muscle
 lumbar subsegment of spinal cord
 triceps brachii muscle
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 |  | More reference expression data | 
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 | BioGPS |  | 
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| Wikidata | 
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Receptor-type tyrosine-protein phosphatase beta or VE-PTP is an enzyme specifically expressed in endothelial cells  that in humans is encoded by the PTPRB gene.[5][6]
Function
VE-PTP is a member of the classical protein tyrosine phosphatase (PTP) family. The deletion of the gene in mouse models was shown to be embryonically lethal,[7] thus indicating that it is important for vasculogenesis and blood vessel development.  In addition, it was shown to participate in adherens junctions complex and regulate vascular permeability.[8][9] Recently, Soni et al. have shown that tyrosine phosphorylation of VE-PTP via Pyk2 kinase downstream of STIM1-induced calcium entry mediates disassembly of the endothelial adherens junctions.[9]
Interactions
VE-PTP contains an extracellular domain composed of multiple fibronectin type_III repeats, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to R3 receptor subtype PTPs. 
The extracellular region was shown to interact with the angiopoietin receptor Tie-2[6] and with the adhesion protein VE-cadherin.[9][10]
VE-PTP was also found to interact with Grb2 and plakoglobin through its cytoplasmatic domain.
VE-PTP was also shown through proximity ligation assay to form a complex with VEGFR2,[11][12] which is involved in regulation of angiogenesis and vascular permeability.[13] Activation of VEGFR2 by VEGF was shown to induce complex dissociation, leading to increased VEGFR2 phosphorylation at tyrosine sites 1175 and 951 in immortalized endothelial cells.[11][12]
Role in disease
Dysregulation of PTPRB correlates with the development of a variety of tumors. PTPRB promotes metastasis of colorectal cancer cells via inducing epithelial-mesenchymal transition (EMT).[14]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000127329 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020154 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: PTPRB protein tyrosine phosphatase, receptor type, B".
- ^ a b Fachinger G, Deutsch U, Risau W (October 1999). "Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2". Oncogene. 18 (43): 5948–5953. doi:10.1038/sj.onc.1202992. PMID 10557082.
- ^ Bäumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, et al. (June 2006). "Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development". Blood. 107 (12): 4754–4762. doi:10.1182/blood-2006-01-0141. PMID 16514057.
- ^ Broermann A, Winderlich M, Block H, Frye M, Rossaint J, Zarbock A, et al. (November 2011). "Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo". The Journal of Experimental Medicine. 208 (12): 2393–2401. doi:10.1084/jem.20110525. PMC 3256962. PMID 22025303.
- ^ a b c Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, et al. (June 2017). "Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca2+ entry regulates disassembly of adherens junctions". American Journal of Physiology. Lung Cellular and Molecular Physiology. 312 (6): L1003 – L1017. doi:10.1152/ajplung.00008.2017. PMC 5495943. PMID 28385807.
- ^ Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, et al. (September 2002). "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts". The EMBO Journal. 21 (18): 4885–4895. doi:10.1093/emboj/cdf497. PMC 126293. PMID 12234928.
- ^ a b Hayashi, Makoto; Majumdar, Arindam; Li, Xiujuan; Adler, Jeremy; Sun, Zuyue; Vertuani, Simona; Hellberg, Carina; Mellberg, Sofie; Koch, Sina; Dimberg, Anna; Young Koh, Gou; Dejana, Elisabetta; Belting, Heinz-Georg; Affolter, Markus; Thurston, Gavin (2013-04-09). "VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation". Nature Communications. 4 (1): 1672. Bibcode:2013NatCo...4.1672H. doi:10.1038/ncomms2683. ISSN 2041-1723. PMC 3644080. PMID 23575676.
- ^ a b Mellberg, Sofie; Dimberg, Anna; Bahram, Fuad; Hayashi, Makoto; Rennel, Emma; Ameur, Adam; Westholm, Jakub Orzechowski; Larsson, Erik; Lindahl, Per; Cross, Michael J.; Claesson-Welsh, Lena (2009). "Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis". The FASEB Journal. 23 (5): 1490–1502. doi:10.1096/fj.08-123810. ISSN 0812-3810. PMID 19136612.
- ^ Abhinand, Chandran S.; Raju, Rajesh; Soumya, Sasikumar J.; Arya, Prabha S.; Sudhakaran, Perumana R. (2016-12-01). "VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis". Journal of Cell Communication and Signaling. 10 (4): 347–354. doi:10.1007/s12079-016-0352-8. ISSN 1873-961X. PMC 5143324. PMID 27619687.
- ^ Weng X, Chen W, Hu W, Xu K, Qi L, Chen J, et al. (April 2019). "PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition". Cell Death & Disease. 10 (5): 352. doi:10.1038/s41419-019-1554-9. PMC 6491493. PMID 31040266.
 
Further reading
- Ramachandran C, Aebersold R, Tonks NK, Pot DA (May 1992). "Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatases". Biochemistry. 31 (17): 4232–4238. doi:10.1021/bi00132a012. PMID 1373652.
- Harder KW, Anderson LL, Duncan AM, Jirik FR (1993). "The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-->q21". Cytogenetics and Cell Genetics. 61 (4): 269–270. doi:10.1159/000133419. PMID 1486802.
- Krueger NX, Streuli M, Saito H (October 1990). "Structural diversity and evolution of human receptor-like protein tyrosine phosphatases". The EMBO Journal. 9 (10): 3241–3252. doi:10.1002/j.1460-2075.1990.tb07523.x. PMC 552056. PMID 2170109.
- Gaits F, Li RY, Ragab A, Ragab-Thomas JM, Chap H (October 1995). "Increase in receptor-like protein tyrosine phosphatase activity and expression level on density-dependent growth arrest of endothelial cells". The Biochemical Journal. 311 ( Pt 1) (Pt 1): 97–103. doi:10.1042/bj3110097. PMC 1136124. PMID 7575486.
- Feito MJ, Bragardo M, Buonfiglio D, Bonissoni S, Bottarel F, Malavasi F, Dianzani U (August 1997). "gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules". International Immunology. 9 (8): 1141–1147. doi:10.1093/intimm/9.8.1141. PMID 9263011.
- Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, et al. (September 2002). "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts". The EMBO Journal. 21 (18): 4885–4895. doi:10.1093/emboj/cdf497. PMC 126293. PMID 12234928.
 
| PDB gallery | 
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			2ahs: Crystal Structure of the Catalytic Domain of Human Tyrosine Receptor Phosphatase Beta
			
			2h02: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
			
			2h03: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
			
			2h04: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
			
			2hc1: Engineered catalytic domain of protein tyrosine phosphatase HPTPbeta.
			
			2hc2: Engineered protein tyrosine phosphatase beta catalytic domain
			
			2i3r: Engineered catalytic domain of protein tyrosine phosphatase HPTPbeta
			
			2i3u: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
			
			2i4e: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
			
			2i4g: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with a sulfamic acid (soaking experiment)
			
			2i4h: Structural studies of protein tyrosine phosphatase beta catalytic domain co-crystallized with a sulfamic acid inhibitor
			
			2i5x: Engineering the PTPbeta catalytic domain with improved crystallization properties |