Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling
Autor: | Stefan Günther, Frederike A. Hartl, Liz Cerqueira, Esmeralda Beck-Garcia, Susana Minguet, Piyamaporn Wipa, Prapat Suriyaphol, Wolfgang W. A. Schamel, Jatuporn Ngoenkam, Burkhart Schraven, Sutatip Pongcharoen, Pussadee Paensuwan, Pankaj Mishra |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
conformation
CD3 Complex CD3 T cell RK motif Receptors Antigen T-Cell chemical and pharmacologic phenomena Article Jurkat Cells medicine NCK2 Humans Src family kinase Phosphorylation lcsh:QH301-705.5 Adaptor Proteins Signal Transducing Oncogene Proteins ZAP-70 Protein-Tyrosine Kinase biology Chemistry ZAP70 T-cell receptor Signal transducing adaptor protein hemic and immune systems Nck General Medicine Cell biology Lck medicine.anatomical_structure lcsh:Biology (General) Lymphocyte Specific Protein Tyrosine Kinase p56(lck) biology.protein TCR Protein Binding Signal Transduction |
Zdroj: | Cells, Vol 10, Iss 834, p 834 (2021) Cells Volume 10 Issue 4 |
ISSN: | 2073-4409 |
Popis: | The T cell antigen receptor (TCR) is expressed on T cells, which orchestrate adaptive immune responses. It is composed of the ligand-binding clonotypic TCRαβ heterodimer and the non-covalently bound invariant signal-transducing CD3 complex. Among the CD3 subunits, the CD3ε cytoplasmic tail contains binding motifs for the Src family kinase, Lck, and the adaptor protein, Nck. Lck binds to a receptor kinase (RK) motif and Nck binds to a proline-rich sequence (PRS). Both motifs only become accessible upon ligand binding to the TCR and facilitate the recruitment of Lck and Nck independently of phosphorylation of the TCR. Mutations in each of these motifs cause defects in TCR signaling and T cell activation. Here, we investigated the role of Nck in proximal TCR signaling by silencing both Nck isoforms, Nck1 and Nck2. In the absence of Nck, TCR phosphorylation, ZAP70 recruitment, and ZAP70 phosphorylation was impaired. Mechanistically, this is explained by loss of Lck recruitment to the stimulated TCR in cells lacking Nck. Hence, our data uncover a previously unknown cooperative interaction between Lck and Nck to promote optimal TCR signaling. |
Databáze: | OpenAIRE |
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