Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex.
Nat Immunol
; 7(1): 57-66, 2006 Jan.
Article
em En
| MEDLINE
| ID: mdl-16327786
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 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Linfócitos T
/
Proteínas Proto-Oncogênicas pp60(c-src)
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Proteínas Proto-Oncogênicas c-cbl
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Ano de publicação:
2006
Tipo de documento:
Article