TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction.
Human Toll-like receptor (TLR) 3 recognizes double-stranded (ds) RNA and induces production of interferon (IFN)-beta independent of the adaptor molecules MyD88 and TIRAP. Thus, another adaptor must exist that preferentially mediates TLR3-dependent production of IFN-beta. We have identified an alternative adaptor, designated Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule (TICAM)-1, that can physically bind the TIR domain of TLR3 and activate the IFN-beta promoter in response to poly(I):poly(C). Thus, dsRNA-TLR3-dependent production of IFN-beta is mediated mainly by TICAM-1. This TICAM-1-dependent pathway may have a role in other TLR-IFN-beta pathways, which form part of the MyD88-independent cellular immune response.
Oshiumi
Hiroyuki
H
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Japan.
Matsumoto
Misako
M
Funami
Kenji
K
Akazawa
Takashi
T
Seya
Tsukasa
T
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007111:Immunity, Cellular; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000096:biosynthesis*; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C494232:IRF3 protein, human; C494233:Irf3 protein, mouse; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C470409:TICAM1 protein, human; C434984:TIRAP protein, human; C499045:TIRAP protein, mouse; C495344:TLR3 protein, human