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Human Interaction Network Ontology
Last uploaded:
June 27, 2014
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| Id | http://purl.obolibrary.org/obo/HINO_0022354
http://purl.obolibrary.org/obo/HINO_0022354
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|---|---|
| Preferred Name | IRAK1 recruits IKK complex |
| Definitions |
The role of IRAK1 kinase activity in the activation of NF-kappa-B by IL-1/TLR is still uncertain. It has been shown that a kinase-dead IRAK1 mutants can still activate NF-kappa-B. Furthermore, stimulation of IRAK1-deficient I1A 293 cells with LMP1 (latent membrane protein 1- a known viral activator of NF-kappa-B) leads to TRAF6 polyubiquitination and IKKbeta activation [Song et al 2006]. On the other hand, IRAK1 enhances p65 Ser536 phosphorylation [Song et al 2006] and p65 binding to the promoter of NF-kappa-B dependent target genes [Liu G et al 2008].<p> IRAK1 has also been shown to be itself Lys63-polyubiquitinated (probably by Pellino proteins, which have E3 ligase activity). Mutation of the ubiquitination sites on IRAK1 prevented interaction with the NEMO subunit of IKK complex and subsequent IL-1/TLR-induced NF-kappa-B activation [Conze et al 2008]. These data suggest that kinase activity of IRAK1 is not essential for its ability to activate NF-kappa-B, while its Lys63-polyubuquitination allows IRAK1 to bind NEMO thus facilitating association of TRAF6 and TAK1 complex with IKK complex followed by induction of NF-kappa-B. </p><p>Upon IL-1/TLR stimulation IRAK1 protein can undergo covalent modifications including phosphorylation [Kollewe et al 2004], ubiquitination [Conze DB et al 2008] and sumoylation [Huang et al 2004]. Depending upon the nature of its modification, IRAK1 may perform distinct functions including activation of IRF5/7 [Uematsu et al 2005, Schoenemeyer et al 2005], NF-kappa-B [Song et al 2006], and Stat1/3 [Huang et al 2004, Nguyen et al 2003].
Reviewed: Napetschnig, Johanna, 2012-11-16
Edited: Shamovsky, V, 2012-11-06
Reviewed: Gillespie, ME, 2010-11-30
Authored: Shamovsky, V, 2010-06-01
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| Type | http://www.w3.org/2002/07/owl#Class |
All Properties
| label |
IRAK1 recruits IKK complex
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|---|---|
| comment |
The role of IRAK1 kinase activity in the activation of NF-kappa-B by IL-1/TLR is still uncertain. It has been shown that a kinase-dead IRAK1 mutants can still activate NF-kappa-B. Furthermore, stimulation of IRAK1-deficient I1A 293 cells with LMP1 (latent membrane protein 1- a known viral activator of NF-kappa-B) leads to TRAF6 polyubiquitination and IKKbeta activation [Song et al 2006]. On the other hand, IRAK1 enhances p65 Ser536 phosphorylation [Song et al 2006] and p65 binding to the promoter of NF-kappa-B dependent target genes [Liu G et al 2008].<p> IRAK1 has also been shown to be itself Lys63-polyubiquitinated (probably by Pellino proteins, which have E3 ligase activity). Mutation of the ubiquitination sites on IRAK1 prevented interaction with the NEMO subunit of IKK complex and subsequent IL-1/TLR-induced NF-kappa-B activation [Conze et al 2008]. These data suggest that kinase activity of IRAK1 is not essential for its ability to activate NF-kappa-B, while its Lys63-polyubuquitination allows IRAK1 to bind NEMO thus facilitating association of TRAF6 and TAK1 complex with IKK complex followed by induction of NF-kappa-B. </p><p>Upon IL-1/TLR stimulation IRAK1 protein can undergo covalent modifications including phosphorylation [Kollewe et al 2004], ubiquitination [Conze DB et al 2008] and sumoylation [Huang et al 2004]. Depending upon the nature of its modification, IRAK1 may perform distinct functions including activation of IRF5/7 [Uematsu et al 2005, Schoenemeyer et al 2005], NF-kappa-B [Song et al 2006], and Stat1/3 [Huang et al 2004, Nguyen et al 2003].
Reviewed: Napetschnig, Johanna, 2012-11-16
Edited: Shamovsky, V, 2012-11-06
Reviewed: Gillespie, ME, 2010-11-30
Authored: Shamovsky, V, 2010-06-01
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| prefLabel |
IRAK1 recruits IKK complex
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| located_in | |
| definition source |
Pubmed14661019
Pubmed18347055
Pubmed15767370
Reactome, http://www.reactome.org
Pubmed12856330
Pubmed18276832
Pubmed14625308
Pubmed15695821
Pubmed16477006
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| prefixIRI |
HINO:0022354
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| seeAlso |
Reactome Database ID Release 43937039
ReactomeREACT_24918
GENE ONTOLOGYGO:0043123
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| subClassOf | |
| type | |
| has_part |
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