TI  - Early events in TNF signaling: a story of associations and dissociations.
PG  - 559-66
AB  - At the cellular level, the multifunctional cytokine tumor necrosis factor
      (TNF) modulates growth and activates genes through various intermediates,
      including protein kinases, protein phosphatases, reactive oxygen
      intermediates, phospholipases, proteases, sphingomyelinases, and
      transcription factors. Unlike many cytokine receptors, however, the
      cytoplasmic domain (CD) of the TNF receptors lacks an intrinsic protein
      kinase activity and yet on interaction with ligand it phosphorylates
      various proteins. Although the kinetics of most of these activities
      differ, their interactions are coordinated through the selective interplay
      between the CD of the receptors and the associated proteins. A unique
      pathway has been identified by the ability of the TNF receptors to
      associate with a novel family of proteins. Two distinct families of
      proteins have emerged, the TNF receptor-associated factors (TRAFs) and the
      death domain homologues. The cloning of members of these gene families and
      the identification of the protein-interaction motifs found within their
      gene products has initiated the molecular identity of factors ( <prot>TRADD</prot> ,
       <prot>FADD</prot>/<prot>MORT</prot> ,  <prot>RIP</prot> ,  <prot>FLICE</prot>/<prot>MACH</prot> , and  TRAFs ) associated with both of the <prot>p60</prot> and
      <prot>p80</prot> forms of the      TNF receptor      and with other members of the TNF receptor
      superfamily. In this review, we summarize these and other TNF
      receptor-associated proteins and their potential roles in regulating the
      activation of <prot>nuclear factor-kappaB</prot> and apoptosis, two major responses
      activated by engagement of TNF receptors by the ligand.
AD  - Department of Molecular Oncology, The University of Texas M. D. Anderson
