Publication: Cooperative interaction of Nck and Lck orchestrates optimal TCR signaling
Issued Date
2021-04-01
Resource Type
ISSN
20734409
Other identifier(s)
2-s2.0-85105180744
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cells. Vol.10, No.4 (2021)
Suggested Citation
Frederike A. Hartl, Jatuporn Ngoenkam, Esmeralda Beck-Garcia, Liz Cerqueira, Piyamaporn Wipa, Pussadee Paensuwan, Prapat Suriyaphol, Pankaj Mishra, Burkhart Schraven, Stefan Günther, Sutatip Pongcharoen, Wolfgang W.A. Schamel, Susana Minguet Cooperative interaction of Nck and Lck orchestrates optimal TCR signaling. Cells. Vol.10, No.4 (2021). doi:10.3390/cells10040834 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78285
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Cooperative interaction of Nck and Lck orchestrates optimal TCR signaling
Abstract
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.