The PAK1 autoregulatory domain is required for interaction with NIK in Helicobacter pylori-induced NF-kappaB activation

Biol Chem. 2006 Jan;387(1):79-86. doi: 10.1515/BC.2006.011.

Abstract

Helicobacter pylori, the etiological agent of various human gastric diseases, induces the transcription factor nuclear factor kappaB (NF-kappaB) and proinflammatory cytokines/chemokines. We have characterised the direct interaction between p21-activated kinase 1 (PAK1) and NF-kappaB-inducing kinase (NIK) in H. pylori-infected epithelial cells. The dimerisation (DI) motif, which is part of the NH2-terminal autoregulatory domain of PAK1, is critical for this interaction, whereas NIK forms complexes with PAK1 through its carboxy-terminal IkappaB kinase alpha (IKKalpha) binding site. Since the identified interaction sites are also crucial for the binding of activator (Rac/Cdc42 in the case of PAK1) or effector molecules (IKKalpha in the case of NIK), sequential stepwise signalling is suggested. Furthermore, we show that mitogen-activated protein kinase kinase kinases (MAP3K), like TPL2 (tumour progression locus 2) and transforming growth factor beta-activated kinase 1 (TAK1), have no impact on H. pylori-induced activation of NF-kappaB. These results identify the roles of PAK1 and NIK in a unique pathway involved in H. pylori-induced NF-kappaB activation, which is crucial for the induction of the innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Gastric Mucosa / cytology
  • Helicobacter pylori / metabolism*
  • Homeostasis
  • Humans
  • I-kappa B Kinase / metabolism
  • Immunity, Innate
  • NF-kappa B / metabolism*
  • Protein Structure, Tertiary / physiology
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • p21-Activated Kinases

Substances

  • NF-kappa B
  • PAK1 protein, human
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • I-kappa B Kinase
  • NF-kappa B kinase