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 th at signals through the endothelial cell-specific Tie2 receptor tyrosin e kinase. Like Vascular endothelial growth factor, Ang1 is essential f or 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 o verexpression of Ang2 disrupts blood vessel formation in the mouse emb ryo. in adult mice and humans, Ang2 is expressed only at sites of vasc ular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acti ng on Tie2 emphasizes the need for exquisite regulation of this angiog enic receptor system.