TY - JOUR
T1 - Recruitment of Nck by CD3ε reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation
AU - Gil, Diana
AU - Schamel, Wolfgang W.A.
AU - Montoya, María
AU - Sánchez-Madrid, Francisco
AU - Alarcón, Balbino
N1 - Funding Information:
We wish to thank Michael Reth, Xosé Bustelo, and Andrés Alcover for providing reagents and Miguel Alonso, Simon Bartlett, Manuel Fresno, Raif Geha, Ed Palmer, Man-Sun Sy, and Karen Willard-Gallo for critically reading the manuscript. We are also indebted to Toñi Cerrato for her expert technical assistance. This work has been supported by grant PM1998-0132 from Comisión Interministerial de Ciencia y Tecnologı́a, grant 08.3/0033.1/2000 from Comunidad de Madrid, and by funds from the Fundación Ramón Areces to the Centro de Biologı́a Molecular. D.G. was a recipient of a Ministerio de Educación fellowship and W.W.A.S. of Marie-Curie grant HPMF-CT-1999-00177.
PY - 2002/6/28
Y1 - 2002/6/28
N2 - How membrane receptors initiate signal transduction upon ligand binding is a matter of intense scrutiny. The T cell receptor complex (TCR-CD3) is composed of TCRα/β ligand binding subunits bound to the CD3 subunits responsible for signal transduction. Although it has long been speculated that TCR-CD3 may undergo a conformational change, confirmation is still lacking. We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ε and results in recruitment of the adaptor protein Nck. This occurs earlier than and independently of tyrosine kinase activation. Finally, by interfering with Nck-CD3ε association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation.
AB - How membrane receptors initiate signal transduction upon ligand binding is a matter of intense scrutiny. The T cell receptor complex (TCR-CD3) is composed of TCRα/β ligand binding subunits bound to the CD3 subunits responsible for signal transduction. Although it has long been speculated that TCR-CD3 may undergo a conformational change, confirmation is still lacking. We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ε and results in recruitment of the adaptor protein Nck. This occurs earlier than and independently of tyrosine kinase activation. Finally, by interfering with Nck-CD3ε association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation.
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U2 - 10.1016/S0092-8674(02)00799-7
DO - 10.1016/S0092-8674(02)00799-7
M3 - Article
C2 - 12110186
AN - SCOPUS:0037188899
SN - 0092-8674
VL - 109
SP - 901
EP - 912
JO - Cell
JF - Cell
IS - 7
ER -