PTPRB

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,{{cite journal | vauthors = Bäumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, Wolburg H, Wolburg-Buchholz K, Deutsch U, Vestweber D | display-authors = 6 | title = Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development | journal = Blood | volume = 107 | issue = 12 | pages = 4754–4762 | date = June 2006 | pmid = 16514057 | doi = 10.1182/blood-2006-01-0141 | doi-access = free }} 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.{{cite journal | vauthors = Broermann A, Winderlich M, Block H, Frye M, Rossaint J, Zarbock A, Cagna G, Linnepe R, Schulte D, Nottebaum AF, Vestweber D | display-authors = 6 | title = Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo | journal = The Journal of Experimental Medicine | volume = 208 | issue = 12 | pages = 2393–2401 | date = November 2011 | pmid = 22025303 | pmc = 3256962 | doi = 10.1084/jem.20110525 }} 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.{{cite journal | vauthors = Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C | display-authors = 6 | title = Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca²⁺ entry regulates disassembly of adherens junctions | journal = American Journal of Physiology. Lung Cellular and Molecular Physiology | volume = 312 | issue = 6 | pages = L1003–L1017 | date = June 2017 | pmid = 28385807 | pmc = 5495943 | doi = 10.1152/ajplung.00008.2017 }}

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 and with the adhesion protein VE-cadherin.{{cite journal | vauthors = Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D | display-authors = 6 | title = VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts | journal = The EMBO Journal | volume = 21 | issue = 18 | pages = 4885–4895 | date = September 2002 | pmid = 12234928 | pmc = 126293 | doi = 10.1093/emboj/cdf497 }}

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,{{Cite journal |last1=Hayashi |first1=Makoto |last2=Majumdar |first2=Arindam |last3=Li |first3=Xiujuan |last4=Adler |first4=Jeremy |last5=Sun |first5=Zuyue |last6=Vertuani |first6=Simona |last7=Hellberg |first7=Carina |last8=Mellberg |first8=Sofie |last9=Koch |first9=Sina |last10=Dimberg |first10=Anna |last11=Young Koh |first11=Gou |last12=Dejana |first12=Elisabetta |last13=Belting |first13=Heinz-Georg |last14=Affolter |first14=Markus |last15=Thurston |first15=Gavin |date=2013-04-09 |title=VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation |journal=Nature Communications |language=en |volume=4 |issue=1 |pages=1672 |doi=10.1038/ncomms2683 |issn=2041-1723 |pmc=3644080 |pmid=23575676|bibcode=2013NatCo...4.1672H }}{{Cite journal |title=Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis |date=2009 |language=en |doi=10.1096/fj.08-123810 |doi-access=free |issn=0812-3810 |last1=Mellberg |first1=Sofie |last2=Dimberg |first2=Anna |last3=Bahram |first3=Fuad |last4=Hayashi |first4=Makoto |last5=Rennel |first5=Emma |last6=Ameur |first6=Adam |last7=Westholm |first7=Jakub Orzechowski |last8=Larsson |first8=Erik |last9=Lindahl |first9=Per |last10=Cross |first10=Michael J. |last11=Claesson-Welsh |first11=Lena |journal=The FASEB Journal |volume=23 |issue=5 |pages=1490–1502 |pmid=19136612 }} which is involved in regulation of angiogenesis and vascular permeability.{{Cite journal |last1=Abhinand |first1=Chandran S. |last2=Raju |first2=Rajesh |last3=Soumya |first3=Sasikumar J. |last4=Arya |first4=Prabha S. |last5=Sudhakaran |first5=Perumana R. |date=2016-12-01 |title=VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis |journal=Journal of Cell Communication and Signaling |language=en |volume=10 |issue=4 |pages=347–354 |doi=10.1007/s12079-016-0352-8 |issn=1873-961X |pmc=5143324 |pmid=27619687}} 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.

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).{{cite journal | vauthors = Weng X, Chen W, Hu W, Xu K, Qi L, Chen J, Lu D, Shao Y, Zheng X, Ye C, Zheng S | display-authors = 6 | title = PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition | journal = Cell Death & Disease | volume = 10 | issue = 5 | pages = 352 | date = April 2019 | pmid = 31040266 | pmc = 6491493 | doi = 10.1038/s41419-019-1554-9 }}

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• {{cite journal | vauthors = Ramachandran C, Aebersold R, Tonks NK, Pot DA | title = Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatases | journal = Biochemistry | volume = 31 | issue = 17 | pages = 4232–4238 | date = May 1992 | pmid = 1373652 | doi = 10.1021/bi00132a012 }}
• {{cite journal | vauthors = Harder KW, Anderson LL, Duncan AM, Jirik FR | title = The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-->q21 | journal = Cytogenetics and Cell Genetics | volume = 61 | issue = 4 | pages = 269–270 | year = 1993 | pmid = 1486802 | doi = 10.1159/000133419 }}
• {{cite journal | vauthors = Krueger NX, Streuli M, Saito H | title = Structural diversity and evolution of human receptor-like protein tyrosine phosphatases | journal = The EMBO Journal | volume = 9 | issue = 10 | pages = 3241–3252 | date = October 1990 | pmid = 2170109 | pmc = 552056 | doi = 10.1002/j.1460-2075.1990.tb07523.x }}
• {{cite journal | vauthors = Gaits F, Li RY, Ragab A, Ragab-Thomas JM, Chap H | title = Increase in receptor-like protein tyrosine phosphatase activity and expression level on density-dependent growth arrest of endothelial cells | journal = The Biochemical Journal | volume = 311 ( Pt 1) | issue = Pt 1 | pages = 97–103 | date = October 1995 | pmid = 7575486 | pmc = 1136124 | doi = 10.1042/bj3110097 }}
• {{cite journal | vauthors = Feito MJ, Bragardo M, Buonfiglio D, Bonissoni S, Bottarel F, Malavasi F, Dianzani U | title = gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules | journal = International Immunology | volume = 9 | issue = 8 | pages = 1141–1147 | date = August 1997 | pmid = 9263011 | doi = 10.1093/intimm/9.8.1141 | doi-access = free }}
• {{cite journal | vauthors = Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D | display-authors = 6 | title = VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts | journal = The EMBO Journal | volume = 21 | issue = 18 | pages = 4885–4895 | date = September 2002 | pmid = 12234928 | pmc = 126293 | doi = 10.1093/emboj/cdf497 }}

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{{PDB Gallery|geneid=5787}}

{{Protein tyrosine phosphatases}}

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