Show simple item record

dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorPalsson-McDermott, Eva M.
dc.contributor.authorBowie, Andrew G.
dc.contributor.authorJefferies, Caroline A.
dc.contributor.authorMansell, Ashley S.
dc.contributor.authorBrady, Gerard
dc.contributor.authorBrint, Elizabeth K.
dc.contributor.authorDunne, Aisling
dc.contributor.authorGray, Pearl
dc.contributor.authorHarte, Mary T.
dc.contributor.authorMcMurray, Diane
dc.contributor.authorSmith, Dirk E.
dc.contributor.authorSims, John E.
dc.contributor.authorBird, Timothy A.
dc.contributor.authorO'Neill, Luke A. J.
dc.date2022-08-11T08:09:08.000
dc.date.accessioned2022-08-23T16:18:48Z
dc.date.available2022-08-23T16:18:48Z
dc.date.issued2001-09-07
dc.date.submitted2011-04-07
dc.identifier.citationNature. 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.issn0028-0836 (Linking)
dc.identifier.doi10.1038/35092578
dc.identifier.pmid11544529
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34899
dc.description.abstractThe 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.isoen_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.urlhttp://dx.doi.org/10.1038/35092578
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectAntigens, Differentiation
dc.subjectCarrier Proteins
dc.subjectCell Line
dc.subject*Drosophila Proteins
dc.subjectHumans
dc.subjectInterleukin-1 Receptor-Associated Kinases
dc.subjectLipopolysaccharides
dc.subjectMembrane Glycoproteins
dc.subjectMice
dc.subjectMolecular Sequence Data
dc.subjectMyeloid Differentiation Factor 88
dc.subjectNF-kappa B
dc.subjectProtein Kinases
dc.subjectRNA, Messenger
dc.subjectReceptors, Cell Surface
dc.subject*Receptors, Immunologic
dc.subject*Receptors, Interleukin-1
dc.subjectSequence Homology, Amino Acid
dc.subject*Signal Transduction
dc.subjectToll-Like Receptor 2
dc.subjectToll-Like Receptor 4
dc.subjectToll-Like Receptor 9
dc.subjectToll-Like Receptors
dc.subjectTransfection
dc.subjectXenopus
dc.subjectXenopus Proteins
dc.subjectImmunology and Infectious Disease
dc.titleMal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
dc.typeJournal Article
dc.source.journaltitleNature
dc.source.volume413
dc.source.issue6851
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/126
dc.identifier.contextkey1924832
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.submissionpathinfdis_pp/126
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages78-83


This item appears in the following Collection(s)

Show simple item record