Fluid Shear Stress Activation of IκB Kinase Is Integrin-dependent

• DOI: 10.1074/jbc.273.46.30544
• Publication Date: 2002-07-26T15:13:03Z
• Authors: Indermeet S. Bhullar; Yi-Shuan Li; Hui Miao; Ebrahim Zandi; Mike Kim; John Y.-J. Shyy; Shu Chien
• Keywords: IκB kinase

Vascular endothelial cells (ECs), forming a boundary between the circulating blood and vessel wall, are constantly subjected to fluid shear stress due flow. The aim of this study was determine role recently identified IκB kinases (IKKs) in activation NF-κB elucidate upstream signaling mechanism that mediates IKK activation. Our results demonstrate IKKs ECs activated by rapid transient manner. This is followed degradation translocation into nucleus. Transfection plasmids encoding catalytic inactive mutants IKKs, <i>i.e.</i> hemagglutinin (HA)-IKKα(K44M) HA-IKKβ(K44A), inhibits stress-induced translocation. In addition, constructs antisense <i>i.e.</i>HA-IKKα(AS) HA-IKKβ(AS), attenuate induction promoter driven κB enhancer element. Preincubation EC monolayer with monoclonal anti-α_vβ₃integrin antibody (clone LM609) attenuates IKK. Inhibition tyrosine genistein causes similar down-regulating effect. These suggest integrin-mediated pathway regulates through response stress.