Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
dc.contributor.author | Fitzgerald, Katherine A. | |
dc.contributor.author | Palsson-McDermott, Eva M. | |
dc.contributor.author | Bowie, Andrew G. | |
dc.contributor.author | Jefferies, Caroline A. | |
dc.contributor.author | Mansell, Ashley S. | |
dc.contributor.author | Brady, Gerard | |
dc.contributor.author | Brint, Elizabeth K. | |
dc.contributor.author | Dunne, Aisling | |
dc.contributor.author | Gray, Pearl | |
dc.contributor.author | Harte, Mary T. | |
dc.contributor.author | McMurray, Diane | |
dc.contributor.author | Smith, Dirk E. | |
dc.contributor.author | Sims, John E. | |
dc.contributor.author | Bird, Timothy A. | |
dc.contributor.author | O'Neill, Luke A. J. | |
dc.date | 2022-08-11T08:09:08.000 | |
dc.date.accessioned | 2022-08-23T16:18:48Z | |
dc.date.available | 2022-08-23T16:18:48Z | |
dc.date.issued | 2001-09-07 | |
dc.date.submitted | 2011-04-07 | |
dc.identifier.citation | Nature. 2001 Sep 6;413(6851):78-83. <a href="http://dx.doi.org/10.1038/35092578">Link to article on publisher's site</a> | |
dc.identifier.issn | 0028-0836 (Linking) | |
dc.identifier.doi | 10.1038/35092578 | |
dc.identifier.pmid | 11544529 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/34899 | |
dc.description.abstract | The recognition of microbial pathogens by the innate immune system involves Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns, with TLR-4 mediating the response to lipopolysaccharide from Gram-negative bacteria. All TLRs have a Toll/IL-1 receptor (TIR) domain, which is responsible for signal transduction. MyD88 is one such protein that contains a TIR domain. It acts as an adapter, being involved in TLR-2, TLR-4 and TLR-9 signalling; however, our understanding of how TLR-4 signals is incomplete. Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome. Mal activates NF-kappaB, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. Mal can form homodimers and can also form heterodimers with MyD88. Activation of NF-kappaB by Mal requires IRAK-2, but not IRAK, whereas MyD88 requires both IRAKs. Mal associates with IRAK-2 by means of its TIR domain. A dominant negative form of Mal inhibits NF-kappaB, which is activated by TLR-4 or lipopolysaccharide, but it does not inhibit NF-kappaB activation by IL-1RI or IL-18R. Mal associates with TLR-4. Mal is therefore an adapter in TLR-4 signal transduction. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11544529&dopt=Abstract">Link to Article in PubMed</a> | |
dc.relation.url | http://dx.doi.org/10.1038/35092578 | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Amino Acid Sequence | |
dc.subject | Animals | |
dc.subject | Antigens, Differentiation | |
dc.subject | Carrier Proteins | |
dc.subject | Cell Line | |
dc.subject | *Drosophila Proteins | |
dc.subject | Humans | |
dc.subject | Interleukin-1 Receptor-Associated Kinases | |
dc.subject | Lipopolysaccharides | |
dc.subject | Membrane Glycoproteins | |
dc.subject | Mice | |
dc.subject | Molecular Sequence Data | |
dc.subject | Myeloid Differentiation Factor 88 | |
dc.subject | NF-kappa B | |
dc.subject | Protein Kinases | |
dc.subject | RNA, Messenger | |
dc.subject | Receptors, Cell Surface | |
dc.subject | *Receptors, Immunologic | |
dc.subject | *Receptors, Interleukin-1 | |
dc.subject | Sequence Homology, Amino Acid | |
dc.subject | *Signal Transduction | |
dc.subject | Toll-Like Receptor 2 | |
dc.subject | Toll-Like Receptor 4 | |
dc.subject | Toll-Like Receptor 9 | |
dc.subject | Toll-Like Receptors | |
dc.subject | Transfection | |
dc.subject | Xenopus | |
dc.subject | Xenopus Proteins | |
dc.subject | Immunology and Infectious Disease | |
dc.title | Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction | |
dc.type | Journal Article | |
dc.source.journaltitle | Nature | |
dc.source.volume | 413 | |
dc.source.issue | 6851 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/infdis_pp/126 | |
dc.identifier.contextkey | 1924832 | |
html.description.abstract | <p>The recognition of microbial pathogens by the innate immune system involves Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns, with TLR-4 mediating the response to lipopolysaccharide from Gram-negative bacteria. All TLRs have a Toll/IL-1 receptor (TIR) domain, which is responsible for signal transduction. MyD88 is one such protein that contains a TIR domain. It acts as an adapter, being involved in TLR-2, TLR-4 and TLR-9 signalling; however, our understanding of how TLR-4 signals is incomplete. Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome. Mal activates NF-kappaB, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. Mal can form homodimers and can also form heterodimers with MyD88. Activation of NF-kappaB by Mal requires IRAK-2, but not IRAK, whereas MyD88 requires both IRAKs. Mal associates with IRAK-2 by means of its TIR domain. A dominant negative form of Mal inhibits NF-kappaB, which is activated by TLR-4 or lipopolysaccharide, but it does not inhibit NF-kappaB activation by IL-1RI or IL-18R. Mal associates with TLR-4. Mal is therefore an adapter in TLR-4 signal transduction.</p> | |
dc.identifier.submissionpath | infdis_pp/126 | |
dc.contributor.department | Department of Medicine, Division of Infectious Diseases and Immunology | |
dc.source.pages | 78-83 |