Manfred Neumann, Anna Foryst-Ludwig, Stefanie Klar, Katrin Schweitzer, Michael Naumann
The PAK1 autoregulatory domain is required for interaction with NIK in Helicobacter pylori-induced NF-?B activation
Helicobacter pylori, the etiological agent of various human gastric diseases, induces the transcription factor nuclear factor ?B (NF-?B) and proinflammatory cytokines/chemokines. We have characterised the direct interaction between p21-activated kinase 1 (PAK1) and NF-?B-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 I?B kinase ? (IKK?) 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 (IKK? 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 ?-activated kinase 1 (TAK1), have no impact on H. pylori-induced activation of NF-?B. These results identify the roles of PAK1 and NIK in a unique pathway involved in H. pylori-induced NF-?B activation, which is crucial for the induction of the innate immune response.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 387, 01/2006
Pages: 79 - 86
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