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

Academic Article

Abstract

  • 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. © 2013 Elsevier Inc.
  • Authors

    Digital Object Identifier (doi)

    Pubmed Id

  • 2823902
  • Author List

  • Roa NS; Ordoñez-Rueda D; Chávez-Rios JR; Raman C; García-Zepeda EA; Lozano F; Soldevila G
  • Start Page

  • 52
  • End Page

  • 59
  • Volume

  • 432
  • Issue

  • 1