The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL‐1 signalling pathway
- 14 July 2006
- journal article
- Published by Springer Nature in EMBO Reports
- Vol. 7 (8) , 838-844
- https://doi.org/10.1038/sj.embor.7400754
Abstract
The mechanism by which YopP simultaneously inhibits mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB pathways has been elusive. Ectopic expression of YopP inhibits the activity and ubiquitination of a complex consisting of overexpressed TGF‐β‐activated kinase 1 (TAK1) and its subunit TAK1‐binding protein (TAB)1, but not of MEK kinase 1. YopP, but not the catalytically inactive mutant YopPC172A, also suppresses basal and interleukin‐1‐inducible activation of endogenous TAK1, TAB1 and TAB2. YopP does not affect the interaction of TAK1, TAB1 and TAB2 but inhibits autophosphorylation of TAK1 at Thr 187 and phosphorylation of TAB1 at Ser 438. Glutathione S ‐transferase‐tagged YopP (GST–YopP) binds to MAPK kinase (MAPKK)4 and TAB1 but not to TAK1 or TAB2 in vitro . Furthermore, YopP in synergy with a previously described negative regulatory feedback loop inhibits TAK1 by MAPKK6–p38‐mediated TAB1 phosphorylation. Taken together, these data strongly suggest that YopP binds to TAB1 and directly inhibits TAK1 activity by affecting constitutive TAK1 and TAB1 ubiquitination that is required for autoactivation of TAK1.Keywords
This publication has 31 references indexed in Scilit:
- Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-κB activationThe Journal of Experimental Medicine, 2005
- Essential function for the kinase TAK1 in innate and adaptive immune responsesNature Immunology, 2005
- MEK1-dependent Delayed Expression of Fos-related Antigen-1 Counteracts c-Fos and p65 NF-κB-mediated Interleukin-8 Transcription in Response to Cytokines or Growth FactorsPublished by Elsevier ,2005
- Critical Roles of Threonine 187 Phosphorylation in Cellular Stress-induced Rapid and Transient Activation of Transforming Growth Factor-β-activated Kinase 1 (TAK1) in a Signaling Complex Containing TAK1-binding Protein TAB1 and TAB2Journal of Biological Chemistry, 2005
- Functions of the Yersinia effector proteins in inhibiting host immune responsesCurrent Opinion in Microbiology, 2005
- TAB2 and TAB3 Activate the NF-κB Pathway through Binding to Polyubiquitin ChainsPublished by Elsevier ,2004
- TAB3, a new binding partner of the protein kinase TAK1Biochemical Journal, 2004
- A Resorcylic Acid Lactone, 5Z-7-Oxozeaenol, Prevents Inflammation by Inhibiting the Catalytic Activity of TAK1 MAPK Kinase KinaseJournal of Biological Chemistry, 2003
- TAK1 is Critical for IκB Kinase-mediated Activation of the NF-κB PathwayJournal of Molecular Biology, 2003
- The MAPK Kinase Kinase TAK1 Plays a Central Role in Coupling the Interleukin-1 Receptor to Both Transcriptional and RNA-targeted Mechanisms of Gene RegulationJournal of Biological Chemistry, 2001