| 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.56
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.89 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-26 and with the adhesion protein VE-cadherin.910
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 VEGFR2,1112 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.1112
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
References
- GRCh38: Ensembl release 89: ENSG00000127329 – Ensembl, May 2017
- 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".
- 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.
- 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.
- Hayashi M, Majumdar A, Li X, Adler J, Sun Z, Vertuani S, et al. (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. PMC 3644080. PMID 23575676.
- Mellberg S, Dimberg A, Bahram F, Hayashi M, Rennel E, Ameur A, et al. (May 2009). "Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis". FASEB Journal. 23 (5): 1490–1502. doi:10.1096/fj.08-123810. PMID 19136612.
- Abhinand CS, Raju R, Soumya SJ, Arya PS, Sudhakaran PR (December 2016). "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. 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
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, et al. (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.