Receptor-type tyrosine-protein phosphatase beta or VE-PTP is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

specifically expressed in

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

s that in humans is encoded by the ''PTPRB''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

VE-PTP is a member of the classical

protein tyrosine phosphatase Protein tyrosine phosphatases (EC 3.1.3.48, systematic name protein-tyrosine-phosphate phosphohydrolase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins: : proteintyrosine phosphate + H2O = ...

(PTP) family. The deletion of the gene in mouse models was shown to be embryonically lethal, thus indicating that it is important for

vasculogenesis Vasculogenesis is the process of blood vessel formation, occurring by a ''De novo synthesis, de novo'' production of endothelial cells. It is the first stage of the formation of the vascular network, closely followed by angiogenesis. Process ...

and blood vessel development. In addition, it was shown to participate in

adherens junctions In cell biology, adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions and cell–matrix junctions in epithelial and endothelial tissues, usually more basal ...

complex and regulate

vascular permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the permeability of a blood vessel wall–in other words, the blood vessel wall's capacity to allow for the flow of small molecules ( ...

. Recently, Soni et al. have shown that tyrosine phosphorylation of VE-PTP via Pyk2 kinase downstream of

STIM1 Stromal interaction molecule 1 is a protein that in humans is encoded by the ''STIM1'' gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane. Even though the pr ...

-induced calcium entry mediates disassembly of the endothelial

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 Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from pree ...

receptor

Tie-2 The angiopoietin receptors are receptors that bind angiopoietin. TIE-1 and TIE-2 comprise the cell-surface receptors that bind and are activated by the angiopoietins, (Ang1, Ang2, Ang3, Ang4). The angiopoietins are protein growth factors ...

and with the adhesion protein

VE-cadherin Cadherin-5, or VE-cadherin (vascular endothelial cadherin), also known as CD144 ( Cluster of Differentiation 144), is a type of cadherin. It is encoded by the human gene ''CDH5''. Function VE-cadherin is a classical cadherin from the cadherin ...

. VE-PTP was also found to interact with

Grb2 Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/ cell communication. In humans, the GRB2 protein is encoded by the ''GRB2'' gene. The protein encoded by this gene binds recepto ...

and

plakoglobin Plakoglobin, also known as junction plakoglobin or gamma-catenin, is a protein that in humans is encoded by the ''JUP'' gene. Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a cytoplasmic compon ...

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).

Function

Interactions

Role in disease

References

Further reading