Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells

Abstract

Atherogenesis involves activation of NF-κB in endothelial cells by fluid shear stress. Because this pathway involves integrins, we investigated the involvement of focal adhesion kinase (FAK). We found that FAK was not required for flow-stimulated translocation of the p65 NF-κB subunit to the nucleus but was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1, an NF-κB-dependent gene. NF-κB activation by TNF-α or hydrogen peroxide was FAK independent. Events upstream of NF-κB, including integrin activation, Rac activation, reactive oxygen production, and degradation of IκB, were FAK independent. FAK therefore regulates NF-κB phosphorylation and transcriptional activity in response to flow by a novel mechanism.