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Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex.

The adaptor molecule SLAP and E3 ubiquitin ligase c-Cbl each regulate expression of T cell receptor (TCR)-CD3 on thymocytes. Here we provide genetic and biochemical evidence that both molecules function in the same pathway. TCR-CD3 expression was similar in the absence of SLAP and/or c-Cbl. SLAP and c-Cbl were found to interact, and their expression together downregulated CD3epsilon. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCRzeta ubiquitination and degradation, preventing the accumulation of fully assembled recycling TCR complexes. These studies indicate that SLAP links the E3 ligase activity of c-Cbl to the TCR, allowing for stage-specific regulation of TCR expression.

Pubmed ID: 16327786


  • Myers MD
  • Sosinowski T
  • Dragone LL
  • White C
  • Band H
  • Gu H
  • Weiss A


Nature immunology

Publication Data

January 16, 2006

Associated Grants

  • Agency: NCI NIH HHS, Id: CA72531
  • Agency: NCI NIH HHS, Id: CA987986

Mesh Terms

  • Animals
  • Antigens, CD3
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Jurkat Cells
  • Mice
  • Mice, Mutant Strains
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins pp60(c-src)
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
  • Transfection