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