Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood.
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.
Reusch
P
P
Institute of Molecular Oncology, Tumor Biology Center, Freiburg, Germany.
Barleon
B
B
Weindel
K
K
Martiny-Baron
G
G
Gödde
A
A
Siemeister
G
G
Marmé
D
D
D000818:Animals; D001483:Base Sequence; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism*; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017077:Culture Media, Conditioned; D017931:DNA Primers; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2; D013755:Tetradecanoylphorbol Acetate