My NCBISign In

Display Settings:

Format

Send to:

Choose Destination
    Cell. 2002 Jul 26;110(2):191-202.

    IRAK-M is a negative regulator of Toll-like receptor signaling.

    Kobayashi K, Hernandez LD, Galán JE, Janeway CA Jr, Medzhitov R, Flavell RA.

    Source

    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.

    Abstract

    Toll-like receptors (TLRs) detect microorganisms and protect multicellular organisms from infection. TLRs transduce their signals through MyD88 and the serine/threonine kinase IRAK. The IRAK family consists of two active kinases, IRAK and IRAK-4, and two inactive kinases, IRAK-2 and IRAK-M. IRAK-M expression is restricted to monocytes/macrophages, whereas other IRAKs are ubiquitous. We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. IRAK-M(-/-) cells exhibited increased cytokine production upon TLR/IL-1 stimulation and bacterial challenge, and IRAK-M(-/-) mice showed increased inflammatory responses to bacterial infection. Endotoxin tolerance, a protection mechanism against endotoxin shock, was significantly reduced in IRAK-M(-/-) cells. Thus, IRAK-M regulates TLR signaling and innate immune homeostasis.

    PMID:
    12150927
    [PubMed - indexed for MEDLINE]

    Publication Types, MeSH Terms, Substances, Secondary Source ID

    Publication Types

    MeSH Terms

    Substances

    Secondary Source ID

    LinkOut - more resources

    Full Text Sources

    Other Literature Sources

    Molecular Biology Databases

    Research Materials

    Miscellaneous

      Supplemental Content

      Click here to read

      Related citations

      See reviews... See all...

      Cited by over 100 PubMed Central articles

      See all...

      Related information

      • Related Citations
        Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
      • BioSystems
        Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
      • Gene
        Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
      • Gene (GeneRIF)
        Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
      • Gene (OMIM)
        Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
      • HomoloGene
        HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
      • Nucleotide
        Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
      • Nucleotide (RefSeq)
        NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Nucleotide (Weighted)
        Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
      • OMIM (calculated)
        Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
      • OMIM (cited)
        Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
      • Protein (RefSeq)
        NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Protein (Weighted)
        Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
      • Protein Clusters
        Clusters of related proteins from the Protein Clusters database that cite the current articles. Sources of references in Protein Clusters include the associated Gene and Conserved Domain records as well as NCBI added citations.
      • Substance (MeSH Keyword)
        PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Taxonomy via GenBank
        Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
      • UniGene
        UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
      • Domains
        Conserved Domain Database (CDD) records that cite the current articles. Citations are from the CDD source database records (PFAM, SMART).
      • Protein
        Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
      • GEO Profiles
        Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
      • Cited in PMC
        Full-text articles in the PubMed Central Database that cite the current articles.

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      You are here: NCBI > Literature > PubMed
      Write to the Help Desk