Document Detail


Phosphorylation of Carma1, but not Bcl10, by Akt regulates TCR/CD28-mediated NF-κB induction and cytokine production.
MedLine Citation:
PMID:  24548923     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Previous studies from our group and others have shown that the Akt kinase can contribute to induction of NF-κB by antigen receptor signaling. However, the direct targets of Akt in this pathway are not known. Here we show that Akt-mediated NF-κB activation is mediated at least in part through direct phosphorylation of the adaptor protein Carma1, which we previously demonstrated could interact with Akt in a TCR ligation-dependent manner. The putative Akt phosphorylation sites in Carma1 are distinct from known PKC consensus sites. Mutation of S551, S637 and S645 in Carma1 to non-phosphorylatable residues decreased phosphorylation of GST-Carma1-linker construct by Akt in vitro. In addition, Carma1 S637A/S645A mutants were significantly impaired in their ability to restore TCR-mediated NF-κB activation and IL-2 expression in Carma1-deficient T cells. Thus, our data reveal Carma1 as a novel target for Akt phosphorylation and suggest that Akt-mediated phosphorylation of Carma1 is an additional regulatory mechanism tuning the NF-κB response downstream of antigen receptor and co-stimulatory signaling.
Authors:
Jing Cheng; Kristia S Hamilton; Lawrence P Kane
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-15
Journal Detail:
Title:  Molecular immunology     Volume:  59     ISSN:  1872-9142     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  110-116     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Ltd. All rights reserved.
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