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Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2.

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.

Pubmed ID: 18438411

Authors

  • Kawagoe T
  • Sato S
  • Matsushita K
  • Kato H
  • Matsui K
  • Kumagai Y
  • Saitoh T
  • Kawai T
  • Takeuchi O
  • Akira S

Journal

Nature immunology

Publication Data

June 20, 2008

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI070167

Mesh Terms

  • Animals
  • Interleukin-1 Receptor-Associated Kinases
  • Mice
  • Signal Transduction
  • Toll-Like Receptors