Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex
| Autor: | Margaret D. Myers, Carmen White, Arthur Weiss, Hamid Band, Leonard L. Dragone, Tomasz Sosinowski, Hua Gu |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD3 Complex
T-Lymphocytes Immunoblotting Proto-Oncogene Proteins pp60(c-src) Immunology Receptors Antigen T-Cell macromolecular substances Transfection Jurkat cells Jurkat Cells Mice Ubiquitin hemic and lymphatic diseases Ring finger medicine Animals Humans Immunology and Allergy Proto-Oncogene Proteins c-cbl Receptor biology Chemistry fungi T-cell receptor Flow Cytometry Molecular biology Mice Mutant Strains Ubiquitin ligase enzymes and coenzymes (carbohydrates) medicine.anatomical_structure biology.protein hormones hormone substitutes and hormone antagonists Function (biology) |
| Zdroj: | Nature Immunology. 7:57-66 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/ni1291 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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