ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway
Abstract
Activation of NF-κB as a consequence of signaling through the Toll and IL-1 receptors is a major element of innate immune responses. We report the identification and characterization of a novel intermediate in these signaling pathways that bridges TRAF6 to MEKK-1. This adapter protein, which we have named ECSIT (evolutionarilyconserved signaling intermediate inToll pathways), is specific for the Toll/IL-1 pathways and is a regulator of MEKK-1 processing. Expression of wild-type ECSIT accelerates processing of MEKK-1, whereas a dominant-negative fragment of ECSIT blocks MEKK-1 processing and activation of NF-κB. These results indicate an important role for ECSIT in signaling to NF-κB and suggest that processing of MEKK-1 is required for its function in the Toll/IL-1 pathway.
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↵Corresponding author.
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E-MAIL sankar.ghosh{at}yale.edu; FAX (203) 727-1764.
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- Received May 25, 1999.
- Accepted July 6, 1999.
- Cold Spring Harbor Laboratory Press