Article: article from journal or magazin.
CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation.
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.
Adaptor Proteins, Signal Transducing, Antigens, CD28/physiology, Apoptosis Regulatory Proteins, CARD Signaling Adaptor Proteins, Guanylate Cyclase/physiology, Humans, I-kappa B Kinase, Interleukin-2/biosynthesis, Isoenzymes/physiology, Jurkat Cells, Membrane Microdomains/physiology, Membrane Proteins/physiology, NF-kappa B/metabolism, Neoplasm Proteins/physiology, Protein Kinase C/physiology, Protein-Serine-Threonine Kinases/physiology, Receptors, Antigen, T-Cell/physiology
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