TI  - TNF-dependent recruitment of the protein kinase <prot>RIP</prot> to the <prot>TNF receptor-1</prot>
      signaling complex.
PG  - 387-96
AB  - The death domain of  <prot>tumor necrosis factor (TNF) receptor-1</prot> (<prot>TNFR1</prot>) 
      triggers distinct signaling pathways leading to apoptosis and <prot>NF-kappa B</prot>
      activation through its interaction with the death domain protein  <prot>TRADD</prot> .
      Here, we show that  <prot>TRADD</prot>  interacts strongly with   <prot>RIP</prot>  , another death domain
      protein that was shown previously to associate with  <prot>Fas</prot>  antigen. We also
      show that  <prot>RIP</prot>  is a serine-threonine kinase that is recruited by  <prot>TRADD</prot>  to
      <prot>TNFR1</prot> in a TNF-dependent process. Overexpression of the intact <prot>RIP</prot> protein
      induces both <prot>NF-kappa B</prot> activation and apoptosis. However, expression of
      the death domain of <prot>RIP</prot> Induces apoptosis, but potently inhibits <prot>NF-kappa
      B</prot> activation by TNF. These results suggest that distinct domains of <prot>RIP</prot>
      participate in the TNF signaling cascades leading to apoptosis and
      <prot>NF-kappa B</prot> activation.
AD  - Tularik, Incorporated, South San Francisco, California 94080, USA.
