A requirement for CARMA1 in TCR-induced NF-kappa B activation

Nat Immunol. 2002 Sep;3(9):830-5. doi: 10.1038/ni824. Epub 2002 Aug 5.


Stimulation of the T cell receptor (TCR) complex initiates multiple signaling cascades that lead to the activation of several transcription factors, including the NF-kappa B family members. Although various proximal signaling components of the TCR have been intensively studied, the distal components that mediate TCR-induced NF-kappa B activation remain largely unknown. Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line. Deficiency in CARMA1 (originally known as CARDII) resulted in selectively impaired activation of NF-kappa B induced by the TCR and a consequent defect in interleukin-2 (IL-2) production. Reconstitution of the CARMA1-deficient cells with CARMA1 fully rescued this signaling defect. Together, our results show that CARMA1 is an essential signaling component that mediates TCR-induced NF-kappa B activation.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Apoptosis Regulatory Proteins
  • B-Cell CLL-Lymphoma 10 Protein
  • CARD Signaling Adaptor Proteins
  • Guanylate Cyclase / physiology*
  • Humans
  • Isoenzymes / physiology
  • Jurkat Cells
  • Membrane Proteins / physiology*
  • Mutation
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / physiology
  • Protein Kinase C / physiology
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell / physiology*


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • B-Cell CLL-Lymphoma 10 Protein
  • BCL10 protein, human
  • CARD Signaling Adaptor Proteins
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • CARD11 protein, human
  • Guanylate Cyclase