Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis - PubMed (original) (raw)

doi: 10.1016/s1074-7613(03)00141-9.

Lauren E Wilson, Carola G Vinuesa, Sylvie Lesage, Mathieu Blery, Lisa A Miosge, Matthew C Cook, Edyta M Kucharska, Hiromitsu Hara, Josef M Penninger, Heather Domashenz, Nancy A Hong, Richard J Glynne, Keats A Nelms, Christopher C Goodnow

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• PMID: 12818157
• DOI: 10.1016/s1074-7613(03)00141-9

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Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis

Jesse E Jun et al. Immunity. 2003 Jun.

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Abstract

In a genome-wide ENU mouse mutagenesis screen a recessive mouse mutation, unmodulated, was isolated with profound defects in humoral immune responses, selective deficits in B cell activation by antigen receptors and T cell costimulation by CD28, and gradual development of atopic dermatitis with hyper-IgE. Mutant B cells are specifically defective in forming connections between antigen receptors and two key signaling pathways for immunogenic responses, NF-kappaB and JNK, but signal normally to calcium, NFAT, and ERK. The mutation alters a conserved leucine in the coiled-coil domain of CARMA-1/CARD11, a member of the MAGUK protein family implicated in organizing multimolecular signaling complexes. These results define Carma-1 as a key regulator of the plasticity in antigen receptor signaling that underpins opposing mechanisms of immunity and tolerance.

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Comment in

• The activation of lymphocytes is in their CARMA.
  Abbas AK, Sen R. Abbas AK, et al. Immunity. 2003 Jun;18(6):721-2. doi: 10.1016/s1074-7613(03)00143-2. Immunity. 2003. PMID: 12818152

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