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c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation.

Nature immunology | Dec 26, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12415267

How Cbl family proteins regulate T cell responses is unclear. We found that c-Cbl Cbl-b double knock-out (dKO) T cells became hyperresponsive upon anti-CD3 stimulation, even though the major T cell antigen receptor (TCR) signaling pathways were not enhanced. The dKO T cells did not down-modulate surface TCR after ligand engagement, which resulted in sustained TCR signaling. However, these cells showed normal ligand-independent TCR internalization, and trafficking of internalized TCR to the lysosome compartment after ligand engagement was reduced. These findings show that Cbl family proteins negatively regulate T cell activation by promoting clearance of engaged TCR from the cell surface, a process that is apparently essential for the termination of TCR signals.

Pubmed ID: 12415267 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Animals | Carrier Proteins | Down-Regulation | Ligands | Lymphocyte Activation | Mice | Mice, Knockout | Molecular Sequence Data | Phosphoproteins | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-cbl | Receptors, Antigen, T-Cell | Signal Transduction | T-Lymphocytes | Ubiquitin-Protein Ligases

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Associated grants

  • Agency: NCI NIH HHS, Id: N01-CO-56000

Mouse Genome Informatics (Data, Gene Annotation)

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