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Licensed Unlicensed Requires Authentication Published by De Gruyter January 13, 2006

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

Manfred Neumann, Anna Foryst-Ludwig, Stefanie Klar, Katrin Schweitzer and Michael Naumann
From the journal


Helicobacter pylori, the etiological agent of various human gastric diseases, induces the transcription factor nuclear factor κB (NF-κB) and proinflammatory cytokines/chemokines. We have characterised the direct interaction between p21-activated kinase 1 (PAK1) and NF-κB-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 IκB kinase α (IKKα) 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 (IKKα 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 β-activated kinase 1 (TAK1), have no impact on H. pylori-induced activation of NF-κB. These results identify the roles of PAK1 and NIK in a unique pathway involved in H. pylori-induced NF-κB activation, which is crucial for the induction of the innate immune response.


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Published Online: 2006-01-13
Published in Print: 2006-01-01

©2006 by Walter de Gruyter Berlin New York