P21-activated Kinase 1 Activates the Nuclear Factor κB (NF-κB)-inducing Kinase-IκB Kinases NF-κB Pathway and Proinflammatory Cytokines in Helicobacter pyloriInfection

Abstract

Helicobacter pylori, the causative agent of several human gastric diseases, induces activation of the immediate early response transcription factor nuclear factor kappaB (NF-kappaB), which subsequently triggers release of proinflammatory cytokines in colonized epithelial cells. Here we report that in H. pylori infection p21-activated kinase 1 (PAK1) activates NF-kappaB. Activated PAK1 associates with NF-kappaB-inducing kinase, which upon activation directs the activity of IkappaB kinases to IkappaBalpha. Our results indicate that in epithelial cells PAK1 participates in a unique pathway that links H. pylori-dependent effector molecules to the activation of NF-kappaB and the induction of the innate immune response.