Helicobacter pylori-induced tyrosine phosphorylation of IKKβ contributes to NF-κB activation

Helicobacter pylori, the etiological agent of several human gastric diseases, induces the transcription factor nuclear factor-kappa B (NF-kappa B) in colonized epithelial cells leading to the release of proinflammatory mediators. Activation of NF-kappa B involves the I kappa B kinase (IKK)-complex composed of two catalytic subunits, IKK alpha and IKK beta, and a regulatory scaffold protein, IKK gamma. IKK beta was shown to be essential for NF-kappa B activation in response to a variety of stimuli including H. pylori. In addition to the phosphorylation of serine residues, tyrosine phosphorylation could be crucial for IKK beta activation. Here we provide evidence that IKK beta phosphorylation is induced in lipid rafts (DRM fractions) of H. pylori-infected cells, but not TNF alpha-stimulated cells. Furthermore, H. pylori transiently induces binding of IKK beta to c-Src kinase. Inhibition of c-Src by specific inhibitors as well as knockdown of c-Src by small interfering RNA reduced phosphorylation of I kappa B alpha as well as of p65. Thus, tyrosine-phosphorylated IKK beta contributes at least in part to NF-kappa B activation in response to H. pylori infection.