Receptor-type tyrosine-protein phosphatase beta or VE-PTP is an enzyme specifically expressed in endothelial cells that in humans is encoded by the PTPRBgene.[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.
^ abFachinger 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. PMID10557082.
^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. PMID16514057.
^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. PMID22025303.
^ abcSoni 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. doi:10.1152/ajplung.00008.2017. PMID28385807.
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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. PMID1486802.
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