Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.
Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.
Maisonpierre
P C
PC
Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Suri
C
C
Jones
P F
PF
Bartunkova
S
S
Wiegand
S J
SJ
Radziejewski
C
C
Compton
D
D
McClain
J
J
Aldrich
T H
TH
Papadopoulos
N
N
Daly
T J
TJ
Davis
S
S
Sato
T N
TN
Yancopoulos
G D
GD
D000595:Amino Acid Sequence; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042787:Receptor, TIE-2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; C467629:Angpt1 protein, rat; D016228:Endothelial Growth Factors; D008024:Ligands; D008222:Lymphokines; D008562:Membrane Glycoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2