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

Research output: Contribution to journalArticle

69 Citations (Scopus)

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
StatePublished - Jan 1 2006

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Thymocytes
Ligases
Ubiquitin
T-Cell Antigen Receptor
Proteins
Ubiquitin-Protein Ligases
Ubiquitination
Fingers
Molecular Biology
Down-Regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex. / Myers, Margaret D.; Sosinowski, Tomasz; Dragone, Leonard L.; White, Carmen; Band, Hamid; Gu, Hua; Weiss, Arthur.

In: Nature Immunology, Vol. 7, No. 1, 01.01.2006, p. 57-66.

Research output: Contribution to journalArticle

Myers, Margaret D. ; Sosinowski, Tomasz ; Dragone, Leonard L. ; White, Carmen ; Band, Hamid ; Gu, Hua ; Weiss, Arthur. / Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex. In: Nature Immunology. 2006 ; Vol. 7, No. 1. pp. 57-66.
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