Lipid rafts in T cell receptor signalling .
Lipid rafts in T cell receptor signalling .
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DOI：
10.1080/09687860500453673
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发表时间：
2006-01
影响因子：
--
通讯作者：
Kabouridis, Panagiotis S
中科院分区：
文献类型：
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作者：
Kabouridis, Panagiotis S
已经广泛地研究了通过T细胞受体（TCR）对抗原进行信号传导所涉及的分子事件和蛋白质组分。TCR刺激后信号级联的激活取决于酪氨酸激酶Lck对受体的磷酸化，酪氨酸激酶Lck通过其翻译后修饰定位于质膜的细胞质面。然而，TCR在质膜磷酸化过程中事件的精确顺序仍有待确定。目前描述早期信号事件的理论结合了脂筏的功能，脂筏是质膜上具有不同脂质和蛋白质组成的微区。脂筏参与哺乳动物细胞的多种生物学功能。在T细胞中，在TCR信号传导中具有关键作用的分子，包括Lck，定位于这些结构域。重要的是，不能定位于筏结构域的这些蛋白质的突变形式不能支持TCR的信号传导。使用纯化的抗洗涤剂膜（DRM）和共聚焦显微镜的生化研究表明，刺激后，TCR和LCK的脂筏可能会接近允许受体的磷酸化。此外，有数据表明TCR的磷酸化可能依赖于Lck活性的瞬时增加，该活性在脂筏内发生以启动信号传导。目前的结果和模型脂筏如何调节TCR信号进行了讨论。
The molecular events and the protein components that are involved in signalling by the T cell receptor (TCR) for antigen have been extensively studied. Activation of signalling cascades following TCR stimulation depends on the phosphorylation of the receptor by the tyrosine kinase Lck, which localizes to the cytoplasmic face of the plasma membrane by virtue of its post-translational modification. However, the precise order of events during TCR phosphorylation at the plasma membrane, remains to be defined. A current theory that describes early signalling events incorporates the function of lipid rafts, microdomains at the plasma membrane with distinct lipid and protein composition. Lipid rafts have been implicated in diverse biological functions in mammalian cells. In T cells, molecules with a key role in TCR signalling, including Lck, localize to these domains. Importantly, mutant versions of these proteins which fail to localise to raft domains were unable to support signalling by the TCR. Biochemical studies using purified detergent-resistant membranes (DRM) and confocal microscopy have suggested that upon stimulation, the TCR and Lck-containing lipid rafts may come into proximity allowing phosphorylation of the receptor. Further, there are data suggesting that phosphorylation of the TCR could depend on a transient increase in Lck activity that takes place within lipid rafts to initiate signalling. Current results and a model of how lipid rafts may regulate TCR signalling are discussed.