2026-05-05T11:14:05Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/643042024-12-16T09:02:03Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Wei, Qianru Brzostek, Joanna Sankaran, Shvetha Casas Requena, Javier Hew, Lois Shi-Qi Yap, Jiawei Zhao, Xiang Wojciech, Lukasz Gascoigne, Nicholas R. J. 2024-01-08T14:38:29Z 2024-01-08T14:38:29Z 2020 P Natl Acad Sci Usa 201913334. https://doi.org/10.1073/pnas.1913334117 0027-8424 https://uvadoc.uva.es/handle/10324/64304 10.1073/pnas.1913334117 15809 27 15817 Proceedings of the National Academy of Sciences 117 1091-6490 Producción Científica 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. Ministerio de Singapur de Salud del Consejo Nacional de Investigaciones Médicas mediante su CBRG/0097/2015 y otorgado por la subvención 2014-T2-1-136 del Ministerio de Educación de Singapur. application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0 Attribution-NonCommercial-NoDerivatives 4.0 Internacional Lck bound to coreceptor is less active than free Lck info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion SI