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 BExternal IDs OMIM : 176882 MGI : 97809 HomoloGene : 2125 GeneCards : PTPRB Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 12: 70.52 – 70.64 Mb Chr 10: 116.28 – 116.39 Mb PubMed search[3] [4] Wikidata
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.
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 (Oct 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, Wolburg H, Wolburg-Buchholz K, Deutsch U, Vestweber D (Jun 2006). "Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development" . Blood . 107 (12): 4754–62. doi :10.1182/blood-2006-01-0141 . PMID 16514057 .
^ Broermann A, Winderlich M, Block H, Frye M, Rossaint J, Zarbock A, Cagna G, Linnepe R, Schulte D, Nottebaum AF, Vestweber D (Nov 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): 2393–401. doi :10.1084/jem.20110525 . PMC 3256962 . PMID 22025303 .
^ a b c Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C (Apr 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, Golding M, Shima DT, Deutsch U, Vestweber D (Sep 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 .
Further reading [ ]
Ramachandran C, Aebersold R, Tonks NK, Pot DA (1992). "Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatases". Biochemistry . 31 (17): 4232–8. 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". Cytogenet. Cell Genet . 61 (4): 269–70. doi :10.1159/000133419 . PMID 1486802 .
Krueger NX, Streuli M, Saito H (1990). "Structural diversity and evolution of human receptor-like protein tyrosine phosphatases" . EMBO J . 9 (10): 3241–52. doi :10.1002/j.1460-2075.1990.tb07523.x . PMC 552056 . PMID 2170109 .
Gaits F, Li RY, Ragab A, Ragab-Thomas JM, Chap H (1995). "Increase in receptor-like protein tyrosine phosphatase activity and expression level on density-dependent growth arrest of endothelial cells" . Biochem. J . 311 (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 (1997). "gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules" . Int. Immunol . 9 (8): 1141–7. doi :10.1093/intimm/9.8.1141 . PMID 9263011 .
Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D (2002). "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts" . EMBO J . 21 (18): 4885–95. doi :10.1093/emboj/cdf497 . PMC 126293 . PMID 12234928 .
PDB gallery
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
Class I
Class II Class III Class IV