Filipp Dominik, Zhang Jenny, Leung Bernadine L, Shaw Andrey, Levin Steven D, Veillette Andre, Julius Michael
Sunnybrook and Women's College Health Sciences Centre, and Departmentof Immunology, University of Toronto, Ontario M4N 3M5, Canada.
J Exp Med. 2003 May 5;197(9):1221-7. doi: 10.1084/jem.20022112.
Whether or how the activation of Lck and Fyn during T cell receptor (TCR) signaling is coordinated, and their delivery of function integrated, is unknown. Here we show that lipid rafts function to segregate Lck and Fyn in T cells before activation. Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn. Genetic evidence demonstrates that Fyn activation is strictly dependent on receptor-induced translocation of Lck. These results characterize the interdependence of Lck and Fyn function and establish the spatial and temporal distinctions of their roles in the cellular activation process.
在T细胞受体（TCR）信号传导过程中，Lck和Fyn的激活是否以及如何协调，它们的功能传递如何整合，目前尚不清楚。在此我们表明，脂筏在激活前可将T细胞中的Lck和Fyn分隔开。TCR和CD4的共聚集在数秒内导致脂筏外的Lck激活，随后其易位到脂筏中并激活共定位的Fyn。遗传学证据表明，Fyn的激活严格依赖于受体诱导的Lck易位。这些结果描述了Lck和Fyn功能的相互依赖性，并确立了它们在细胞激活过程中作用的时空差异。
