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CD3ε recruits Numb to promote TCR degradation. CD3ε recruits Numb to promote TCR degradation. Martin-Blanco, N., Jiménez-Teja, D., Bretones, G., Borroto, A., Caraballo, M., Screpanti, I., León, J., Alarcón, B., Canelles, M*2015-10-26T23:00:00Z<p style="text-align:justify;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2"><strong>​Abstract</strong><br></span></p><p style="text-align:justify;"><span class="ms-rteFontSize-2">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 CD3ε that overlaps with the Nck binding site. As a result, Cbl couples specifically to the CD3ε 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.</span><br></p><p><a href="">​Int Immunol. 28:127-137 (2016). PMID: 26507128. </a><br></p>205