Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning.
TIE2 is a receptor-like tyrosine kinase expressed almost exclusively in endothelial cells and early hemopoietic cells and required for the normal development of vascular structures during embryogenesis. We report the identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a novel expression cloning technique that involves intracellular trapping and detection of the ligand in COS cells. The structure of Angiopoietin-1 differs from that of known angiogenic factors or other ligands for receptor tyrosine kinases. Although Angiopoietin-1 binds and induces the tyrosine phosphorylation of TIE2, it does not directly promote the growth of cultured endothelial cells. However, its expression in close proximity with developing blood vessels implicates Angiopoietin-1 in endothelial developmental processes.
Davis
Samuel
S
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Aldrich
Thomas H
TH
Jones
Pamela F
PF
Acheson
Ann
A
Compton
Debra L
DL
Jain
Vivek
V
Ryan
Terence E
TE
Bruno
Joanne
J
Radziejewski
Czeslaw
C
Maisonpierre
Peter C
PC
Yancopoulos
George D
GD
D000595:Amino Acid Sequence; D042683:Angiopoietin-1; D000818:Animals; D002417:Cattle; D002455:Cell Division; D003001:Cloning, Molecular / Q000379:methods*; D004730:Endothelium, Vascular / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D006321:Heart / Q000196:embryology; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000276:immunology; D019000:Phosphotyrosine / Q000378:metabolism; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D051381:Rats; D042787:Receptor, TIE-2; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; C467629:Angpt1 protein, rat; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D010455:Peptides; D011506:Proteins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D042787:Receptor, TIE-2