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Identification of CARDIAK, a RIP-like kinase that associates with caspase-1.

Members of the tumor necrosis factor receptor (TNFR) superfamily have an important role in the induction of cellular signals resulting in cell growth, differentiation and death. TNFR-1 recruits and assembles a signaling complex containing a number of death domain (DD)-containing proteins, including the adaptor protein TRADD and the serine/threonine kinase RIP, which mediates TNF-induced NF-kappa B activation. RIP also recruits caspase-2 to the TNFR-1 signaling complex via the adaptor protein RAIDD, which contains a DD and a caspase-recruiting domain (CARD). Here, we have identified a RIP-like kinase, termed CARDIAK (for CARD-containing interleukin (IL)-1 beta converting enzyme (ICE) associated kinase), which contains a serine/threonine kinase domain and a carboxy-terminal CARD. Overexpression of CARDIAK induced the activation of both NF-kappa B and Jun N-terminal kinase (JNK). CARDIAK interacted with the TNFR-associated factors TRAF-1 and TRAF-2, and a dominant-negative form of TRAF-2 inhibited CARDIAK-induced NF-kappa B activation. Interestingly, CARDIAK specifically interacted with the CARD of caspase-1 (previously known as ICE), and this interaction correlated with the processing of pro-caspase-1 and the formation of the active p20 subunit of caspase-1. Together, these data suggest that CARDIAK may be involved in NF-kappa B/JNK signaling and in the generation of the proinflammatory cytokine IL-1 beta through activation of caspase-1.

Pubmed ID: 9705938

Authors

  • Thome M
  • Hofmann K
  • Burns K
  • Martinon F
  • Bodmer JL
  • Mattmann C
  • Tschopp J

Journal

Current biology : CB

Publication Data

July 16, 1998

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Caspase 1
  • Cell Line, Transformed
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • NF-kappa B
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor
  • Sequence Homology, Amino Acid
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2