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.
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).[11]
Ramachandran C, Aebersold R, Tonks NK, Pot DA (May 1992). "Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatases". Biochemistry. 31 (17): 4232–4238. doi:10.1021/bi00132a012. PMID1373652.
Harder KW, Anderson LL, Duncan AM, Jirik FR (1993). "The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-->q21". Cytogenetics and Cell Genetics. 61 (4): 269–270. doi:10.1159/000133419. PMID1486802.
