PTPRB

PTPRB
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPTPRB, HPTP-BETA, HPTPB, PTPB, R-PTP-BETA, VEPTP, protein tyrosine phosphatase, receptor type B, protein tyrosine phosphatase receptor type B
External IDsOMIM: 176882; MGI: 97809; HomoloGene: 2125; GeneCards: PTPRB; OMA:PTPRB - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 10: 116.28 – 116.39 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

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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

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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

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000127329Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020154Ensembl, 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. ^ 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.
  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. ^ 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.
  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

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