Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation.

Details

Serval ID
serval:BIB_C69E7B2460A0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation.
Journal
Current Biology
Author(s)
Egawa T., Albrecht B., Favier B., Sunshine M.J., Mirchandani K., O'Brien W., Thome M., Littman D.R.
ISSN
0960-9822[print], 0960-9822[linking]
Publication state
Published
Issued date
2003
Volume
13
Number
14
Pages
1252-1258
Language
english
Abstract
Ligation of antigen receptors (TCR, BCR) on T and B lymphocytes leads to the activation of new transcriptional programs and cell cycle progression. Antigen receptor-mediated activation of NF-kappa B, required for proliferation of B and T cells, is disrupted in T cells lacking PKC theta and in B and T cells lacking Bcl10, a caspase recruitment domain (CARD)-containing adaptor protein. CARMA1 (also called CARD11 and Bimp3), the only lymphocyte-specific member in a family of membrane-associated guanylate kinase (MAGUK) scaffolding proteins that interact with Bcl10 by way of CARD-CARD interactions, is required for TCR-induced NF-kappa B activation in Jurkat T lymphoma cells. Here we show that T cells from mice lacking CARMA1 expression were defective in recruitment of Bcl10 to clustered TCR complexes and lipid rafts, in activation of NF-kappa B, and in induction of IL-2 production. Development of CD5(+) peritoneal B cells was disrupted in these mice, as was B cell proliferation in response to both BCR and CD40 ligation. Serum immunoglobulin levels were also markedly reduced in the mutant mice. Together, these results show that CARMA1 has a central role in antigen receptor signaling that results in activation and proliferation of both B and T lymphocytes.
Keywords
Adaptor Proteins, Vesicular Transport/metabolism, Animals, Apoptosis Regulatory Proteins, B-Lymphocytes/metabolism, B-Lymphocytes/physiology, Blotting, Southern, Blotting, Western, CARD Signaling Adaptor Proteins, Chromosome Mapping, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Regulation, Guanylate Kinase, Immunoglobulins/blood, Membrane Proteins, Mice, Mice, Mutant Strains, NF-kappa B/metabolism, Nucleoside-Phosphate Kinase/immunology, Nucleoside-Phosphate Kinase/metabolism, Receptors, Antigen, B-Cell/metabolism, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, T-Lymphocytes/metabolism, T-Lymphocytes/physiology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:11
Last modification date
20/08/2019 15:42
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