Fig. 1

Angiopoietin signaling at the TIE2 receptor. Angiopoietin 1 (ANG1) is constitutively secreted by perivascular mural cells. Ligand-binding of (ANG1) to TIE2 induces sequestration of the tyrosine kinase Src and thus establishes stable expression of VE-cadherin on the surface of the endothelial cell. ANG2 is stored in Weibel-Palade (WBP) bodies and rapidly released upon triggering signals. Its binding to TIE2 abolishes ANG1-induced sequestration of Src, resulting in the internalization of VE-cadherin. Furthermore, sensitizing endothelial cells (EC) for ligands targeting nuclear factor-κB (NF- κB), such as vascular endothelial growth factor or tumor necrosis factor-α, results in the expression of adhesion molecules (selectines, intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM)), which facilitates leukocyte adhesion and transmigration