FIG. 7.

Signaling events mediating thrombin-induced ICAM-1 expression in endothelial cells. Activation of Gα_q and dissociation of Gβγ complex after thrombin stimulation of protease activated receptor-1 (PAR-1) results in the parallel activation of PKCδ and PI3 kinase and the downstream kinase Akt-dependent pathways. These pathways converge to activate IKKβ, which in turn promotes RelA/p65 homodimer binding to the ICAM-1 promoter secondary to phosphorylation and degradation of IκBα. PKC-δ also activates p38 MAP kinase, which induces phosphorylation of RelA/p65, and thereby enhances the transcriptional capacity of the bound RelA/p65. The resultant ICAM-1 expression promotes the stable adhesion of leukocytes to endothelial cells.