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Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the Angiopoietin receptor Tie-2

Oncogene volume 18, pages 5948–5953 (1999)Cite this article

Abstract

During development of the vertebrate vascular system essential signals are transduced via protein-tyrosine phosphorylation. Null-mutations of receptor-tyrosine kinase (RTK) genes expressed in endothelial cells (ECs) display early lethal vascular phenotypes. We aimed to identify endothelial protein-tyrosine phosphatases (PTPs), which should have similar importance in EC-biology. A murine receptor-type PTP was identified by a degenerated PCR cloning approach from endothelial cells (VE-PTP). By in situ hybridization this phosphatase was found to be specifically expressed in vascular ECs throughout mouse development. In experiments using GST-fusion proteins, as well as in transient transfections, trapping mutants of VE-PTP co-precipitated with the Angiopoietin receptor Tie-2, but not with the Vascular Endothelial Growth Factor receptor 2 (VEGFR-2/Flk-1). In addition, VE-PTP dephosphorylates Tie-2 but not VEGFR-2. We conclude that VE-PTP is a Tie-2 specific phosphatase expressed in ECs, and VE-PTP phosphatase activity serves to specifically modulate Angiopoietin/Tie-2 function. Based on its potential role as a regulator of blood vessel morphogenesis and maintainance, VE-PTP is a candidate gene for inherited vascular malformations similar to the Tie-2 gene.

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Acknowledgements

We wish to thank F Kiefer for many valuable suggestions and his constructive criticism of the manuscript. We are grateful to S Esser for reagents and discussions and to TM Schlaeger and S Bamforth for comments on the manuscript. We also thank C Weiss for ACE cells, A Damert for tissue sections, H Schnürch for the brain capillary cDNA library, A Ullrich for the Flk-1 expression vector, H Kataoka for α-Flk-1 mAb 12α1 and H App (SUGEN) for α-Flk-1 antiserum 1D3. This work was funded by the Max-Planck-Society. U Deutsch was supported by the Deutsche Krebshilfe.

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  1. Department of Molecular Cell Biology, Max-Planck-Institute for Physiological and Clinical Research, W.G. Kerckhoff Institute, Parkstrasse 1, Bad Nauheim, D-61231, Germany

    Gregor Fachinger & Urban Deutsch

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  1. Gregor Fachinger
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  2. Urban Deutsch
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Fachinger, G., Deutsch, U. & Risau, W. Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the Angiopoietin receptor Tie-2. Oncogene 18, 5948–5953 (1999). https://doi.org/10.1038/sj.onc.1202992

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