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

Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA. Focal adhesion kinase modulates activation of NF-kappa B by flow in endothelial cells. Am J Physiol Cell Physiol 297: C814-C822, 2009. First published July 8, 2009; doi: 10.1152/ajpcell.00226.2009.-Atherogenesis involves activation of NF-kappa B 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-kappa B subunit to the nucleus but was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1, an NF-kappa B-dependent gene. NF-kappa B activation by TNF-alpha or hydrogen peroxide was FAK independent. Events upstream of NF-kappa B, including integrin activation, Rac activation, reactive oxygen production, and degradation of I kappa B, were FAK independent. FAK therefore regulates NF-kappa B phosphorylation and transcriptional activity in response to flow by a novel mechanism.