TRAF6 is a signal transducer for interleukin-1.
Many cytokines signal through different cell-surface receptors to activate the transcription factor NF-kappaB. Members of the TRAF protein family have been implicated in the activation of NF-kappaB by the tumour-necrosis factor (TNF)-receptor superfamily. Here we report the identification of a new TRAF family member, designated TRAF6. When overexpressed in human 293 cells, TRAF6 activates NF-kappaB. A dominant-negative mutant of TRAF6 inhibits NF-kappaB activation signalled by interleukin-1 (IL-1) but not by TNF. IL-1 treatment of 293 cells induces the association of TRAF6 with IRAK, a serine/threonine kinase that is rapidly recruited to the IL-1 receptor after IL-1 induction. These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling.
Cao
Z
Z
Tularik Inc., South San Francisco, California 94080, USA.
Xiong
J
J
Takeuchi
M
M
Kurama
T
T
Goeddel
D V
DV
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D053592:Interleukin-1 Receptor-Associated Kinases; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D014162:Transfection
D002352:Carrier Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D011506:Proteins; D048029:TNF Receptor-Associated Factor 6; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases