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PMID:12867038
| Citation |
Egawa, T, Albrecht, B, Favier, B, Sunshine, MJ, Mirchandani, K, O'Brien, W, Thome, M and Littman, DR (2003) Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation. Curr. Biol. 13:1252-8 |
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| 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. |
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| 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 |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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