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TAK1 is a ubiquitin-dependent kinase of MKK and IKK

TRAF6 is a signal transducer that activates IB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS). IKK activation by TRAF6 requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA1) an... Full description

Journal Title: Nature 2001, Vol.412(6844), p.346
Main Author: Chen Wang
Other Authors: Li Deng , Mei Hong , Giridhar R. Akkaraju , Jun-Ichiro Inoue , Zhijian J. Chen
Format: Electronic Article Electronic Article
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ID: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/35085597
Link: http://dx.doi.org/10.1038/35085597
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recordid: nature_a10.1038/35085597
title: TAK1 is a ubiquitin-dependent kinase of MKK and IKK
format: Article
creator:
  • Chen Wang
  • Li Deng
  • Mei Hong
  • Giridhar R. Akkaraju
  • Jun-Ichiro Inoue
  • Zhijian J. Chen
subjects:
  • Kinases
  • Activation
  • Chains
  • Pathways
  • Purification
  • Equivalence
  • Copyrights
  • Transducers
  • Proteins
  • Enzymes
  • Catalysis
  • Stresses
  • General and Nonclassified (MD)
  • General and Nonclassified (EC)
  • General and Nonclassified (Ed)
  • General and Nonclassified (Ep)
  • Surveying, Theory, and Analysis (CE)
  • Design Principles, Theory, and Analysis (Mt)
  • Computing Milieux (General) (Ci)
  • Electronics and Communications Milieux (General) (Ea)
  • Solid State Milieux (General) (So)
  • Article
ispartof: Nature, 2001, Vol.412(6844), p.346
description: TRAF6 is a signal transducer that activates IB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS). IKK activation by TRAF6 requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA1) and TRIKA2 (ref. 5). TRIKA1 is a dimeric ubiquitin-conjugating enzyme complex composed of Ubc13 and Uev1A (or the functionally equivalent Mms2). This Ubc complex, together with TRAF6, catalyses the formation of a Lys 63 (K63)-linked polyubiquitin chain that mediates IKK activation through a unique proteasome-independent mechanism. Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. Moreover, the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination. We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK.
language:
source:
identifier: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/35085597
fulltext: fulltext
issn:
  • 0028-0836
  • 00280836
  • 1476-4687
  • 14764687
url: Link


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titleTAK1 is a ubiquitin-dependent kinase of MKK and IKK
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descriptionTRAF6 is a signal transducer that activates IB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS). IKK activation by TRAF6 requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA1) and TRIKA2 (ref. 5). TRIKA1 is a dimeric ubiquitin-conjugating enzyme complex composed of Ubc13 and Uev1A (or the functionally equivalent Mms2). This Ubc complex, together with TRAF6, catalyses the formation of a Lys 63 (K63)-linked polyubiquitin chain that mediates IKK activation through a unique proteasome-independent mechanism. Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. Moreover, the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination. We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK.
subjectKinases ; Activation ; Chains ; Pathways ; Purification ; Equivalence ; Copyrights ; Transducers ; Proteins ; Enzymes ; Catalysis ; Stresses ; General and Nonclassified (MD) ; General and Nonclassified (EC) ; General and Nonclassified (Ed) ; General and Nonclassified (Ep) ; Surveying, Theory, and Analysis (CE) ; Design Principles, Theory, and Analysis (Mt) ; Computing Milieux (General) (Ci) ; Electronics and Communications Milieux (General) (Ea) ; Solid State Milieux (General) (So) ; Article;
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