title: Helicobacter pylori-induced tyrosine phosphorylation of IKKβ contributes to NF-κB activation.
abstract: Helicobacter pylori, the etiological agent of several human gastric diseases, induces the transcription factor nuclear factor-κB (NF-κB) in colonized epithelial cells leading to the release of proinflammatory mediators. Activation of NF-κB involves the IκB kinase (IKK)-complex composed of two catalytic subunits, IKKα and IKKβ, and a regulatory scaffold protein, IKKγ. IKKβ was shown to be essential for NF-κB 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 IKKβ activation. Here we provide evidence that IKKβ phosphorylation is induced in lipid rafts (DRM fractions) of H. pylori-infected cells, but not TNFα-stimulated cells. Furthermore, H. pylori transiently induces binding of IKKβ 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 IκBα as well as of p65. Thus, tyrosine-phosphorylated IKKβ contributes at least in part to NF-κB activation in response to H. pylori infection.
authors.affiliation: Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rieke
authors.forename: Anja
authors.initials: A
authors.lastname: Papendieck
authors.forename: Olga
authors.initials: O
authors.lastname: Sokolova
authors.forename: Michael
authors.initials: M
authors.lastname: Naumann
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry* / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism / Q000821:virology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: D051996:Transcription Factor RelA; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D051550:I-kappa B Kinase