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

Nelly S. Roa, Diana Ordoñez-Rueda, Jesús R. Chávez-Rios, Chander Raman, Eduardo A. García-Zepeda, Francisco Lozano, Gloria Soldevila

Producción: Contribución a una revistaArtículorevisión exhaustiva

10 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)52-59
Número de páginas8
PublicaciónBiochemical and Biophysical Research Communications
Volumen432
N.º1
DOI
EstadoPublicada - 01 mar. 2013

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