CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation

Nat Immunol. 2002 Sep;3(9):836-43. doi: 10.1038/ni830. Epub 2002 Aug 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Apoptosis Regulatory Proteins
  • B-Cell CLL-Lymphoma 10 Protein
  • CARD Signaling Adaptor Proteins
  • CD28 Antigens / physiology
  • 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 Kinase C-theta
  • Protein-Serine-Threonine Kinases / physiology
  • Receptors, Antigen, T-Cell / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • B-Cell CLL-Lymphoma 10 Protein
  • BCL10 protein, human
  • CARD Signaling Adaptor Proteins
  • CD28 Antigens
  • Interleukin-2
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • CARD11 protein, human
  • Guanylate Cyclase