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- Title
Essential function for the kinase TAK1 in innate and adaptive immune responses.
- Authors
Sato, Shintaro; Sanjo, Hideki; Takeda, Kiyoshi; Ninomiya-Tsuji, Jun; Yamamoto, Masahiro; Kawai, Taro; Matsumoto, Kunihiro; Takeuchi, Osamu; Akira, Shizuo
- Abstract
Transforming growth factor-beta-activated kinase 1 (TAK1) has been linked to interleukin 1 receptor and tumor necrosis factor receptor signaling. Here we generated mouse strains with conditional expression of a Map3k7 allele encoding part of TAK1. TAK1-deficient embryonic fibroblasts demonstrated loss of responses to interleukin 1beta and tumor necrosis factor. Studies of mice with B cell-specific TAK1 deficiency showed that TAK1 was indispensable for cellular responses to Toll-like receptor ligands, CD40 and B cell receptor crosslinking. In addition, antigen-induced immune responses were considerably impaired in mice with B cell-specific TAK1 deficiency. TAK1-deficient cells failed to activate transcription factor NF-kappaB and mitogen-activated protein kinases in response to interleukin 1beta, tumor necrosis factor and Toll-like receptor ligands. However, TAK1-deficient B cells were able to activate NF-kappaB but not the kinase Jnk in response to B cell receptor stimulation. These results collectively indicate that TAK1 is key in the cellular response to a variety of stimuli.
- Publication
Nature immunology, 2005, Vol 6, Issue 11, p1087
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1255