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Essential function for the kinase TAK1 in innate and adaptive immune responses.

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.

Pubmed ID: 16186825

Authors

  • Sato S
  • Sanjo H
  • Takeda K
  • Ninomiya-Tsuji J
  • Yamamoto M
  • Kawai T
  • Matsumoto K
  • Takeuchi O
  • Akira S

Journal

Nature immunology

Publication Data

November 21, 2005

Associated Grants

None

Mesh Terms

  • Animals
  • Antigens, CD40
  • B-Lymphocytes
  • Embryo, Mammalian
  • Fibroblasts
  • Gene Deletion
  • Immunity, Innate
  • Interleukin-17
  • Lymphopoiesis
  • MAP Kinase Kinase Kinases
  • Membrane Glycoproteins
  • Mice
  • Mice, Mutant Strains
  • NF-kappa B
  • Receptors, Antigen, B-Cell
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha