Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood

Angiogenesis. 2001;4(2):123-31. doi: 10.1023/a:1012226627813.


The transmembrane tyrosine kinase TIE-2, the receptor for the angiopoietins-1 and -2, has been shown to be involved in angiogenic processes. Investigating the regulation of TIE-2 expression on endothelial cells, we found that stimulators such as PMA induce a decrease of TIE-2 protein from the cell surface without affecting TIE-2 mRNA. In conditioned media of PMA stimulated endothelial cells, a soluble form of this receptor comprising parts of the extracellular domain can be detected. Using a sandwich ELISA, we were able to detect and quantify TIE-2 receptors in cell lysates (representing the whole transmembrane receptor) and in cell culture supernatants (representing a soluble form of this receptor, sTIE-2). Several factors influencing the shedding process e.g. basic FGF could be identified. Finally, the soluble form of TIE-2 could also be detected in human biological fluids such as sera and plasma from healthy controls.

MeSH terms

  • Animals
  • Base Sequence
  • Culture Media, Conditioned
  • DNA Primers
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / metabolism*
  • Precipitin Tests
  • Proto-Oncogene Proteins*
  • Receptor, TIE-2
  • Tetradecanoylphorbol Acetate / pharmacology


  • Culture Media, Conditioned
  • DNA Primers
  • MEN1 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Receptor, TIE-2
  • Tetradecanoylphorbol Acetate