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

Oncogene. 1999 Oct 21;18(43):5948-53. doi: 10.1038/sj.onc.1202992.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Endothelium, Vascular / enzymology*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, TIE-2
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Nerve Tissue Proteins
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2
  • Receptors, Vascular Endothelial Growth Factor
  • PTPRZ1 protein, human
  • Protein Tyrosine Phosphatases
  • Ptprz1 protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5