loading...| Preferred Name | MyD88:Mal cascade initiated on plasma membrane | |
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| Definitions |
Edited: Shamovsky, V, 2012-11-05 The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects. Authored: de Bono, B, 2005-08-16 10:54:15 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Reviewed: Napetschnig, Johanna, 2012-11-16 Reviewed: Gillespie, ME, 2010-11-30 |
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| ID |
http://purl.obolibrary.org/obo/HINO_0022313 |
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| comment |
Edited: Shamovsky, V, 2012-11-05 The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects. Authored: de Bono, B, 2005-08-16 10:54:15 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Reviewed: Napetschnig, Johanna, 2012-11-16 Reviewed: Gillespie, ME, 2010-11-30 |
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| definition source |
Reactome, http://www.reactome.org Pubmed15276183 |
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| label |
MyD88:Mal cascade initiated on plasma membrane |
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| prefixIRI |
HINO:0022313 |
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| prefLabel |
MyD88:Mal cascade initiated on plasma membrane |
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| seeAlso |
Reactome Database ID Release 43166058 GENE ONTOLOGYGO:0002755 ReactomeREACT_6788 |
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| has_part |
http://purl.obolibrary.org/obo/HINO_0009132 http://purl.obolibrary.org/obo/HINO_0009130 http://purl.obolibrary.org/obo/HINO_0015703 http://purl.obolibrary.org/obo/HINO_0015704 http://purl.obolibrary.org/obo/HINO_0022346 http://purl.obolibrary.org/obo/HINO_0009140 http://purl.obolibrary.org/obo/HINO_0009141 http://purl.obolibrary.org/obo/HINO_0009143 http://purl.obolibrary.org/obo/HINO_0009142 http://purl.obolibrary.org/obo/HINO_0009331 http://purl.obolibrary.org/obo/HINO_0022354 http://purl.obolibrary.org/obo/HINO_0009151 http://purl.obolibrary.org/obo/HINO_0009152 http://purl.obolibrary.org/obo/HINO_0009153 http://purl.obolibrary.org/obo/HINO_0009150 http://purl.obolibrary.org/obo/HINO_0009127 http://purl.obolibrary.org/obo/HINO_0009125 http://purl.obolibrary.org/obo/HINO_0009120 http://purl.obolibrary.org/obo/HINO_0009129 |