CARMA1 is a critical lipid raft–associated regulator of TCR-induced NF-κB activation
- 5 August 2002
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 3 (9) , 836-843
- https://doi.org/10.1038/ni830
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-κB activation and IL-2 production and on the c-Jun NH2-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-κB activation and CD28 costimulation–dependent Jnk activation.Keywords
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