TICAM-1, an Adaptor Molecule That Participates in Toll-like Receptor 3-mediated Interferon-Beta Induction

Nat Immunol. 2003 Feb;4(2):161-7. doi: 10.1038/ni886. Epub 2003 Jan 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / immunology*
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation / metabolism
  • Binding Sites
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins*
  • Female
  • Gene Silencing
  • Humans
  • Immunity, Cellular
  • Interferon Regulatory Factor-3
  • Interferon-beta / biosynthesis*
  • Male
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88
  • NF-kappa B / metabolism
  • Pregnancy
  • Protein Structure, Tertiary
  • RNA, Double-Stranded / metabolism
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism
  • Receptors, Interleukin-1 / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tissue Distribution
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Antigens, Differentiation
  • DNA-Binding Proteins
  • Drosophila Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • MYD88 protein, human
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • RNA, Double-Stranded
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • TICAM-1 protein, mouse
  • TICAM1 protein, human
  • TIRAP protein, human
  • TIRAP protein, mouse
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Transcription Factor AP-1
  • Transcription Factors
  • Interferon-beta

Associated data

  • GENBANK/AB086380
  • GENBANK/AB091053