PTPRB explained

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.^{[1] [2]}

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,^[3] 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.^[4] 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.^[5]

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.^{[5] [6]}

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).^[7]

References

Further reading

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

Notes and References

1. Web site: Entrez Gene: PTPRB protein tyrosine phosphatase, receptor type, B .
2. Fachinger G, Deutsch U, Risau W . Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2 . Oncogene . 18 . 43 . 5948–5953 . October 1999 . 10557082 . 10.1038/sj.onc.1202992 . free .
3. Bäumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, Wolburg H, Wolburg-Buchholz K, Deutsch U, Vestweber D . 6 . Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development . Blood . 107 . 12 . 4754–4762 . June 2006 . 16514057 . 10.1182/blood-2006-01-0141 . free .
4. Broermann A, Winderlich M, Block H, Frye M, Rossaint J, Zarbock A, Cagna G, Linnepe R, Schulte D, Nottebaum AF, Vestweber D . 6 . 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 . 2393–2401 . November 2011 . 22025303 . 3256962 . 10.1084/jem.20110525 .
5. Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C . 6 . 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 . 312 . 6 . L1003–L1017 . June 2017 . 28385807 . 5495943 . 10.1152/ajplung.00008.2017 .
6. Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D . 6 . VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts . The EMBO Journal . 21 . 18 . 4885–4895 . September 2002 . 12234928 . 126293 . 10.1093/emboj/cdf497 .
7. Weng X, Chen W, Hu W, Xu K, Qi L, Chen J, Lu D, Shao Y, Zheng X, Ye C, Zheng S . 6 . PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition . Cell Death & Disease . 10 . 5 . 352 . April 2019 . 31040266 . 6491493 . 10.1038/s41419-019-1554-9 .