A schematic depicting the signaling pathways through which the Ang-1/Tie-2 receptor pathway regulates IL-8 production in HUVECs. Exposure to Ang-1 activates Tie-2 receptors which, in turn, provoke activation of the p38, Erk1/2, SAPK/JNK, and the PI-3 kinase pathways. While the Erk1/2 and SAPK/JNK pathways promote c-Jun phosphorylation and AP-1 activation leading to IL-8 induction, the mechanisms through which the PI-3 kinase pathway modulates IL-8 induction in response to Ang-1 are unclear, since this pathway didn't influence c-Jun phosphorylation. Also illustrated is the negative effect of the p38 MAPK pathway on Erk1/2 phosphorylation.