RT info:eu-repo/semantics/article
T1 Lck bound to coreceptor is less active than free Lck
A1 Wei, Qianru
A1 Brzostek, Joanna
A1 Sankaran, Shvetha
A1 Casas, Javier
A1 Hew, Lois Shi-Qi
A1 Yap, Jiawei
A1 Zhao, Xiang
A1 Wojciech, Lukasz
A1 Gascoigne, Nicholas R. J.
AB Src family kinase Lck plays critical roles during T cell development and activation, as it phosphorylates the TCR/CD3 complex to initiate TCR signaling. Lck is present either in coreceptor-bound or coreceptor-unbound (free) forms, and we here present evidence that the two pools of Lck have different molecular properties. We discovered that the free Lck fraction exhibited higher mobility than CD8α-bound Lck in OT-I T hybridoma cells. The free Lck pool showed more activating Y394 phosphorylation than the coreceptor-bound Lck pool. Consistent with this, free Lck also had higher kinase activity, and free Lck mediated higher T cell activation as compared to coreceptor-bound Lck. Furthermore, the coreceptor-Lck coupling was independent of TCR activation. These findings give insights into the initiation of TCR signaling, suggesting that changes in coreceptor-Lck coupling constitute a mechanism for regulation of T cell sensitivity.
SN 0027-8424
YR 2020
FD 2020
LK https://uvadoc.uva.es/handle/10324/64304
UL https://uvadoc.uva.es/handle/10324/64304
LA eng
NO P Natl Acad Sci Usa 201913334. https://doi.org/10.1073/pnas.1913334117
NO Producción Científica
DS UVaDOC
RD 12-jul-2024