T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

Guilin Qiao; Zhenping Li; Luciana Molinero; Maria-Luisa Alegre; Haiyan Ying; Zuoming Sun; Josef M Penninger; Jian Zhang

doi:10.1128/MCB.01505-07

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T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

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T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b

Guilin Qiao, Zhenping Li, Luciana Molinero, Maria-Luisa Alegre, Haiyan Ying, Zuoming Sun, Josef M Penninger and Jian Zhang

Molecular and cellular biology, Vol.28(7), pp.2470-2480

04/01/2008

DOI: 10.1128/MCB.01505-07

PMCID: PMC2268433

PMID: 18227156

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https://www.ncbi.nlm.nih.gov/pmc/articles/2268433View

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Abstract

ABSTRACT It has previously been shown that E3 ubiquitin ligase Casitas B-lineage lymphoma-b (Cbl-b) negatively regulates T-cell activation, but the molecular mechanism(s) underlying this inhibition is not completely defined. In this study, we report that the loss of Cbl-b selectively results in aberrant activation of NF-κB upon T-cell antigen receptor (TCR) ligation, which is mediated by phosphatidylinositol 3-kinase (PI3-K)/Akt and protein kinase C-θ (PKC-θ). TCR-induced hyperactivation of Akt in the absence of Cbl-b may potentiate the formation of caspase recruitment domain-containing membrane-associated guanylate kinase protein 1 (CARMA1)-B-cell lymphoma/leukemia 10 (Bcl10)-mucosa-associated lymphatic tissue 1(MALT1) (CBM) complex, which appears to be independent of PKC-θ. Cbl-b associates with PKC-θ upon TCR stimulation and regulates TCR-induced PKC-θ activation via Vav-1, which couples PKC-θ to PI3-K and allows it to be phosphorylated. PKC-θ then couples IκB kinases (IKKs) to the CBM complex, resulting in the activation of the IKK complex. Therefore, our data provide the first evidence to demonstrate that the down-regulation of TCR-induced NF-κB activation by Cbl-b is mediated coordinately by both Akt-dependent and PKC-θ-dependent signaling pathways in primary T cells.

Details

Title: Subtitle: T-Cell Receptor-Induced NF-κB Activation Is Negatively Regulated by E3 Ubiquitin Ligase Cbl-b
Creators: Guilin Qiao - Sections of Nephrology, Committee on Immunology, The University of Chicago, 5841 S. Maryland Ave., Chicago, Illinois 60637
Zhenping Li - Sections of Nephrology
Luciana Molinero - Rheumatology, Department of Medicine, Committee on Immunology, The University of Chicago, 5841 S. Maryland Ave., Chicago, Illinois 60637
Maria-Luisa Alegre - Rheumatology, Department of Medicine, Committee on Immunology, The University of Chicago, 5841 S. Maryland Ave., Chicago, Illinois 60637
Haiyan Ying - Sections of Nephrology, Committee on Immunology, The University of Chicago, 5841 S. Maryland Ave., Chicago, Illinois 60637
Zuoming Sun - Department of Microbiology and Immunology, University of Illinois at Chicago, 835 S. Wolcott, Chicago, Chicago, Illinois 60612
Josef M Penninger - Institute of Molecular Biotechnology, The Austrian Academy of Sciences, 1030 Vienna, Austria
Jian Zhang - Sections of Nephrology, Committee on Immunology, The University of Chicago, 5841 S. Maryland Ave., Chicago, Illinois 60637
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.28(7), pp.2470-2480
DOI: 10.1128/MCB.01505-07
PMID: 18227156
PMCID: PMC2268433
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Language: English
Date published: 04/01/2008
Academic Unit: Pathology
Record Identifier: 9984047733102771

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