Lck bound to coreceptor is less active than free Lck

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...

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Detalles Bibliográficos
Autores: Wei, Qianru, Brzostek, Joanna, Sankaran, Shvetha, Casas, Javier, Shi-Qi Hew, Lois, Yap, Jiawei, Zhao, Xiang, Wojciech, Lukasz, Gascoigne, Nicholas R. J.
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/226403
Acceso en línea:http://hdl.handle.net/10261/226403
Access Level:acceso abierto
Palabra clave:Lck
Coreceptor
T cell signaling
T cell receptor
T cell development
Descripción
Sumario: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.