PTPRB

PTPRB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AHS, 2H02, 2H03, 2H04, 2HC1, 2HC2, 2I3R, 2I3U, 2I4E, 2I4G, 2I4H, 2I5X
Identifiers
Aliases	PTPRB , HPTP-BETA, HPTPB, PTPB, R-PTP-BETA, VEPTP, protein tyrosine phosphatase, receptor type B, protein tyrosine phosphatase receptor type B
External IDs	OMIM: 176882 MGI: 97809 HomoloGene: 2125 GeneCards: PTPRB
Gene location (Human) Chr. Chromosome 12 (human) [1] Band 12q15 Start 70,515,870 bp [1] End 70,637,440 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 D2 Start 116,275,523 bp [2] End 116,389,535 bp [2]
RNA expression pattern Bgee Top expressed in visceral pleura upper lobe of lung metanephric glomerulus lung right ventricle right lung ventricle parietal pleura myocardium upper lobe of left lung More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein tyrosine phosphatase activity phosphatase activity transmembrane receptor protein tyrosine phosphatase activity GO:0001948 protein binding phosphoprotein phosphatase activity hydrolase activity Cellular component integral component of membrane receptor complex integral component of plasma membrane membrane plasma membrane specific granule membrane tertiary granule membrane Biological process phosphate-containing compound metabolic process protein dephosphorylation angiogenesis dephosphorylation peptidyl-tyrosine dephosphorylation neutrophil degranulation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5787	19263
Ensembl	ENSG00000127329	ENSMUSG00000020154
UniProt	P23467	B2RU80
RefSeq (mRNA)	NM_001109754 NM_001206971 NM_001206972 NM_002837 NM_001330204	NM_029928
RefSeq (protein)	NP_001103224 NP_001193900 NP_001193901 NP_001317133 NP_002828	NP_084204
Location (UCSC)	Chr 12: 70.52 – 70.64 Mb	Chr 10: 116.28 – 116.39 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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). ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000127329 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020154 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: PTPRB protein tyrosine phosphatase, receptor type, B".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.