The carboxy-terminal region of CD5 is required for c-CBL mediated TCR signaling downmodulation in thymocytes
| Autor: | Chander Raman, Francisco Lozano, Diana Ordoñez-Rueda, Nelly S. Roa, Eduardo A. García-Zepeda, Jesús R. Chávez-Ríos, Gloria Soldevila |
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| Rok vydání: | 2013 |
| Předmět: |
CD3
Molecular Sequence Data Biophysics Receptors Antigen T-Cell Down-Regulation chemical and pharmacologic phenomena macromolecular substances Biology CD5 Antigens Biochemistry Mice Ubiquitin immune system diseases hemic and lymphatic diseases Animals Amino Acid Sequence Proto-Oncogene Proteins c-cbl Binding site Phosphorylation Molecular Biology Cells Cultured Sequence Deletion Mice Inbred BALB C Thymocytes T-cell receptor hemic and immune systems Cell Biology Ubiquitin ligase Cell biology Protein Structure Tertiary Thymocyte biology.protein Signal transduction Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 432(1) |
| ISSN: | 1090-2104 |
| Popis: | CD5 functions as a negative regulator of TCR signaling during thymocyte development, however, the molecular mechanisms involved in this process remain elusive. A key molecule involved in the down modulation of TCR signaling is c-Cbl, an ubiquitin ligase that physically associates with CD5. Crosslinking of TCR in thymocytes leads to ubiquitylation and lysosomal/proteasomal degradation of TCR downstream signaling effectors and CD5 itself. The present report shows that co-engagement of CD3 with CD5 enhanced c-Cbl phosphorylation, which was not affected by the deletion of the pseudo-ITAM domain of CD5, the putative binding site for c-Cbl. However, amino acids present in the carboxy-terminal region of CD5, were necessary for this effect, indicating that ITAM-independent sites were involved in the interaction of c-Cbl with CD5. The carboxy-terminal region of CD5 was also required for Vav degradation, a well-known target for c-Cbl-dependent ubiquitylation. These results support the notion that the distal cytoplasmic domain of CD5, including Y463, plays a relevant role in the downmodulation of TCR signals in thymocytes via c-Cbl. |
| Databáze: | OpenAIRE |
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