title: Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2.
abstract: Members of the IRAK family of kinases mediate Toll-like receptor (TLR) signaling. Here we show that IRAK2 was essential for sustaining TLR-induced expression of genes encoding cytokines and activation of the transcription factor NF-kappaB, despite the fact that IRAK2 was dispensable for activation of the initial signaling cascades. IRAK2 was activated 'downstream' of IRAK4, like IRAK1, and TLR-induced cytokine production was abrogated in the absence of both IRAK1 and IRAK2. Whereas the kinase activity of IRAK1 decreased within 1 h of TLR2 stimulation, coincident with IRAK1 degradation, the kinase activity of IRAK2 was sustained and peaked at 8 h after stimulation. Thus, IRAK2 is critical in late-phase TLR responses, and IRAK1 and IRAK2 are essential for the initial responses to TLR stimulation.
authors.affiliation: Laboratory of Host Defense, World Premier International Research Center, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Tatsukata
authors.initials: T
authors.lastname: Kawagoe
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Matsushita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsui
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D000818:Animals; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D051193:Toll-Like Receptors; D053592:Interleukin-1 Receptor-Associated Kinases