The carboxy-terminal region of CD5 is required for c-CBL mediated TCR signaling downmodulation in thymocytes.

Autor: Roa NS; Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF 04510, Mexico., Ordoñez-Rueda D, Chávez-Rios JR, Raman C, García-Zepeda EA, Lozano F, Soldevila G
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2013 Mar 01; Vol. 432 (1), pp. 52-9. Date of Electronic Publication: 2013 Jan 30.
DOI: 10.1016/j.bbrc.2013.01.086
Abstrakt: 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.
(Copyright © 2013 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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