CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation
- PMID: 12154360
- DOI: 10.1038/ni830
CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation
Abstract
CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation.
Comment in
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Up the down staircase.Nat Immunol. 2002 Sep;3(9):802-3. doi: 10.1038/ni0902-802. Nat Immunol. 2002. PMID: 12205467 No abstract available.
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