Regulation of NF-kappaB activation in T cells via association of the adapter proteins ADAP and CARMA1

Science. 2007 May 4;316(5825):754-8. doi: 10.1126/science.1137895.

Abstract

The adapter protein ADAP regulates T lymphocyte adhesion and activation. We present evidence for a previously unrecognized function for ADAP in regulating T cell receptor (TCR)-mediated activation of the transcription factor NF-kappaB. Stimulation of ADAP-deficient mouse T cells with antibodies to CD3 and CD28 resulted in impaired nuclear translocation of NF-kappaB, a reduced DNA binding, and delayed degradation and decreased phosphorylation of IkappaB (inhibitor of NF-kappaB). TCR-stimulated assembly of the CARMA1-BCL-10-MALT1 complex was substantially impaired in the absence of ADAP. We further identified a region of ADAP that is required for association with the CARMA1 adapter and NF-kappaB activation but is not required for ADAP-dependent regulation of adhesion. These findings provide new insights into ADAP function and the mechanism by which CARMA1 regulates NF-kappaB activation in T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • B-Cell CLL-Lymphoma 10 Protein
  • CARD Signaling Adaptor Proteins / metabolism*
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Caspases / metabolism
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Humans
  • I-kappa B Proteins / metabolism
  • Isoenzymes / metabolism
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Mutation
  • Neoplasm Proteins / metabolism
  • Protein Kinase C / metabolism
  • Protein Kinase C-theta
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell / immunology
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transcription Factor RelA / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • CARD Signaling Adaptor Proteins
  • CD28 Antigens
  • CD3 Complex
  • Card11 protein, mouse
  • Fyb protein, mouse
  • I-kappa B Proteins
  • Isoenzymes
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Rela protein, mouse
  • Transcription Factor RelA
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • Caspases
  • Malt1 protein, mouse
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein