title: TICAM-1 and TICAM-2: toll-like receptor adapters that participate in induction of type 1 interferons.
abstract: Toll-like receptor (TLR) 3 and 4 mediate the expression of many genes, including NF-kappaB- and interferon-regulatory factor (IRF)-3/interferon (IFN)-inducible genes, in macrophages and dendritic cells (DCs) in response to their ligand stimuli, polyI:C and lipopolysaccharide (LPS). Toll-IL-1 receptor homology domain (TIR)-containing adapter molecule 1 (TICAM-1) facilitates expression of IFN-inducible genes via TLR3. Although MyD88 and Mal/TIRAP adapters function downstream of TLR4, they barely induce IFN-beta. In addition, DC maturation as well as IFN-beta induction are largely independent of MyD88 and Mal/TIRAP. TICAM-1 is the functional adapter for both TLR3 and TLR4 that induces type 1 IFN and MyD88-independent DC maturation. In LPS-mediated TLR4 activation, a complex of TICAM-1 and an additional TLR4-binding adapter serves as the adapter. We named this TLR4-TICAM-1-bridging adapter TICAM-2. Our results reveal the details of MyD88-independent pathways which separately recruit the distinct adapters downstream of TLR3 and TLR4 and variations of the TLR output are in part regulated by the two additional adapters in DCs.
authors.affiliation: Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan. seya-tu@med.hokudai.ac.jp
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oshiumi
authors.forename: Miwa
authors.initials: M
authors.lastname: Sasai
authors.forename: Takashi
authors.initials: T
authors.lastname: Akazawa
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014777:Virus Diseases / Q000276:immunology; D014780:Viruses / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C470409:TICAM1 protein, human; C480228:TICAM2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors