Journal article
Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex
Science (American Association for the Advancement of Science), Vol.321(5889), pp.663-668
08/01/2008
DOI: 10.1126/science.1157340
PMCID: PMC2669719
PMID: 18635759
Abstract
Cytokine signaling is thought to require assembly of multi-component signaling complexes at cytoplasmic segments of membrane-embedded receptors, in which receptor-proximal protein kinases are activated. Indeed, CD40, a tumor necrosis factor receptor (TNFR) family member, forms a complex containing adaptor molecules TRAF2 and TRAF3, ubiquitin conjugating enzyme Ubc13, cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2), IκB kinase regulatory subunit IKKγ (also called NEMO) and mitogen-activated protein kinase (MAPK) kinase kinase MEKK1 upon ligation. TRAF2, Ubc13, and IKKγ were required for complex assembly and activation of MEKK1 and MAPK cascades. However, these kinases were not activated unless the multi-component signaling complex translocated from CD40 to the cytosol upon c-IAP1/2-induced degradation of TRAF3. This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling.
Details
- Title: Subtitle
- Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex
- Creators
- Atsushi Matsuzawa - Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA92093-0723, USAPing-Hui Tseng - Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA92093-0723, USASivakumar Vallabhapurapu - Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA92093-0723, USAJun-Li Luo - Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA92093-0723, USAWeizhou Zhang - Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA92093-0723, USAHaopeng Wang - Department of Immunology, St Jude Children’s Research Hospital, Memphis TN 38105-2794, USADario A. A Vignali - Department of Immunology, St Jude Children’s Research Hospital, Memphis TN 38105-2794, USAEwen Gallagher - Department of Immunology and Molecular Pathology, Royal Free & University College, Medical School, Windeyer Building, 46 Cleveland Street, London, W1T 4JF, UKMichael Karin - Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA92093-0723, USA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.321(5889), pp.663-668
- DOI
- 10.1126/science.1157340
- PMID
- 18635759
- PMCID
- PMC2669719
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Language
- English
- Date published
- 08/01/2008
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083282902771
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