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酪氨酸激酶Syk在肥大细胞高亲和力IgE受体信号传导中的关键作用。

Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells.

作者信息

Costello P S, Turner M, Walters A E, Cunningham C N, Bauer P H, Downward J, Tybulewicz V L

机构信息

National Institute for Medical Research, London, UK.

出版信息

Oncogene. 1996 Dec 19;13(12):2595-605.

PMID:9000133
Abstract

Activation of the high affinity IgE receptor (Fc epsilon RI) of mast cells, a member of the antigen receptor family, leads to the release of allergic mediators, a critical event in the onset of immediate hypersensitivity. Stimulation of Fc epsilon RI results in the rapid association and activation of the Syk tyrosine kinase. Using Syk-deficient mast cells we show that they fail to degranulate, synthesize leukotrienes and secrete cytokines when stimulated through Fc epsilon RI, conclusively demonstrating an essential role for Syk in Fc epsilon RI signalling. Furthermore, our data strongly supports a model of Fc epsilon RI engagement leading to the sequential activation of the tyrosine kinases Lyn and then Syk. A similar mechanism is likely to apply to signal transduction through all members of the antigen receptor family.

摘要

肥大细胞的高亲和力IgE受体(FcεRI)作为抗原受体家族的一员,其激活会导致过敏介质的释放,这是速发型超敏反应发生过程中的关键事件。FcεRI的刺激会导致Syk酪氨酸激酶迅速结合并激活。利用缺乏Syk的肥大细胞,我们发现当通过FcεRI刺激时,它们无法脱颗粒、合成白三烯和分泌细胞因子,这确凿地证明了Syk在FcεRI信号传导中起着至关重要的作用。此外,我们的数据有力地支持了一种模型,即FcεRI的结合会导致酪氨酸激酶Lyn先被激活,然后Syk被激活。类似的机制可能适用于通过抗原受体家族所有成员进行的信号转导。

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Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells.酪氨酸激酶Syk在肥大细胞高亲和力IgE受体信号传导中的关键作用。
Oncogene. 1996 Dec 19;13(12):2595-605.
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Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells.在大鼠嗜碱性白血病RBL-2H3细胞的Syk阴性变体中,转染Syk蛋白酪氨酸激酶可重建高亲和力IgE受体介导的脱颗粒作用。
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Direct interaction of Syk and Lyn protein tyrosine kinases in rat basophilic leukemia cells activated via type I Fc epsilon receptors.在通过I型Fcε受体激活的大鼠嗜碱性白血病细胞中,Syk和Lyn蛋白酪氨酸激酶的直接相互作用。
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Regulation of rat basophilic leukemia-2H3 mast cell secretion by a constitutive Lyn kinase interaction with the high affinity IgE receptor (Fc epsilon RI).通过组成型Lyn激酶与高亲和力IgE受体(FcεRI)相互作用对大鼠嗜碱性白血病-2H3肥大细胞分泌的调节
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Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering.酪氨酸激酶与高亲和力IgE受体之间相互作用的重建,这种相互作用受受体聚集的控制。
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Activation of the high-affinity immunoglobulin E receptor Fc epsilon RI in RBL-2H3 cells is inhibited by Syk SH2 domains.Syk SH2结构域可抑制RBL-2H3细胞中高亲和力免疫球蛋白E受体FcεRI的激活。
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Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI.p72syk与免疫球蛋白E高亲和力受体FcεRI的γ和β亚基之间的相互作用。
Mol Cell Biol. 1995 Jan;15(1):272-81. doi: 10.1128/MCB.15.1.272.

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