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

Margaret D. Myers, Tomasz Sosinowski, Leonard L. Dragone, Carmen White, Hamid Band, Hua Gu, Arthur Weiss

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70 Scopus citations

Abstract

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 CD3ε. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCRζ 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.

Original languageEnglish (US)
Pages (from-to)57-66
Number of pages10
JournalNature Immunology
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 1 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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