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Publication : CD3ε recruits Numb to promote TCR degradation.

First Author  Martin-Blanco N Year  2016
Journal  Int Immunol Volume  28
Issue  3 Pages  127-37
PubMed ID  26507128 Mgi Jnum  J:246188
Mgi Id  MGI:5924289 Doi  10.1093/intimm/dxv060
Citation  Martin-Blanco N, et al. (2016) CD3epsilon recruits Numb to promote TCR degradation. Int Immunol 28(3):127-37
abstractText  Modulation of TCR signaling upon ligand binding is achieved by changes in the equilibrium between TCR degradation, recycling and synthesis; surprisingly, the molecular mechanism of such an important process is not fully understood. Here, we describe the role of a new player in the mediation of TCR degradation: the endocytic adaptor Numb. Our data show that Numb inhibition leads to abnormal intracellular distribution and defective TCR degradation in mature T lymphocytes. In addition, we find that Numb simultaneously binds to both Cbl and a site within CD3epsilon that overlaps with the Nck binding site. As a result, Cbl couples specifically to the CD3epsilon chain to mediate TCR degradation. The present study unveils a novel role of Numb that lies at the heart of TCR signaling initiation and termination.
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