Fig 1. Schematic overview of the effect of angiopoietin/Tie2 signaling on endothelial barrier function.

In quiescence (A), angiopoietin-1 (ang-1) is released from pericytes and activates, and thereby phosphorylates tyrosine kinase receptor Tie2. Activation of Tie2 strengthens endothelial barrier function via Rac-1/Rho kinase/vascular endothelial (VE)-cadherin signaling. In contrast, in response to hemorrhagic shock (B) angiopoietin-2 (ang-2) is rapidly released from weibel palade bodies (WPB), leading to increased endothelial permeability via inhibition of Tie2 activation. Other transmembrane proteins that affect Tie2 phosphorylation include Tie1 and vascular endothelial-protein tyrosine phosphatase (VE-PTP), which both inhibit Tie2 phosphorylation upon a stress stimulus.