The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor-kappaB inhibitor ABIN-2.

Tie2 is a receptor tyrosine kinase expressed predominantly in endothelial cells and is essential for blood vessel formation and maintenance. The receptor has potent antiinflammatory effects on endothelial cells, suppressing vascular endothelial growth factor- and tumor necrosis factor-induced expression of leukocyte adhesion molecules and procoagulant tissue factor and inhibiting vascular leakage. To delineate the signaling pathways utilized by Tie2, we performed yeast two-hybrid screening of a human endothelial cell cDNA library and identified a novel protein interacting with the intracellular domain of the receptor.

Vascular endothelial growth factor modulates the Tie-2:Tie-1 receptor complex.

The receptor tyrosine kinase Tie-1 is expressed predominantly in endothelial cells where it physically associates with the related receptor Tie-2. Positive signalling through Tie-2 is associated with microvessel stability and suppression of this signal is thought to be required for vascular endothelial growth factor (VEGF)-induced microvessel remodelling or growth. Here we examine the effects of VEGF on Tie-1 and the Tie-2:Tie-1 complex.