PTPRB

Template:Short description Template:Infobox gene 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.

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, 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. 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.

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 and with the adhesion protein VE-cadherin.

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, which is involved in regulation of angiogenesis and vascular permeability. 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.

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).