IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling.
The interleukin-1 receptor (IL-1R) signaling pathway leads to nuclear factor kappa B (NF-kappaB) activation in mammals and is similar to the Toll pathway in Drosophila: the IL-1R-associated kinase (IRAK) is homologous to Pelle. Two additional proximal mediators were identified that are required for IL-1R-induced NF-kappaB activation: IRAK-2, a Pelle family member, and MyD88, a death domain-containing adapter molecule. Both associate with the IL-1R signaling complex. Dominant negative forms of either attenuate IL-1R-mediated NF-kappaB activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation.
Muzio
M
M
University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA.
Ni
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Feng
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Dixit
V M
VM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000943:Antigens, Differentiation; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D053592:Interleukin-1 Receptor-Associated Kinases; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D002352:Carrier Proteins; D029721:Drosophila Proteins; D007375:Interleukin-1; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011506:Proteins; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D048029:TNF Receptor-Associated Factor 6; D011494:Protein Kinases; C079896:pll protein, Drosophila; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases