Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation.
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 TCR alpha/beta 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 CD3 epsilon and results in recruitment of the adaptor protein Nck. This occurs earlier than and independently of tyrosine kinase activation. Finally, by interfering with Nck-CD3 epsilon association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antigen-Presenting Cells, Antigens, CD3, Binding Sites, Humans, Jurkat Cells, Ligands, Lymphocyte Activation, Mice, Molecular Sequence Data, Oncogene Proteins, Phosphorylation, Phosphotyrosine, Proline, Protein Binding, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, src Homology Domains
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antigen-Presenting Cells, Antigens, CD3, Binding Sites, Humans, Jurkat Cells, Ligands, Lymphocyte Activation, Mice, Molecular Sequence Data, Oncogene Proteins, Phosphorylation, Phosphotyrosine, Proline, Protein Binding, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, src Homology Domains
Cell
Date: Jun. 28, 2002
PubMed ID: 12110186
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