Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils
Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils
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Lyn 和 Syk 酪氨酸激酶预防人嗜酸性粒细胞细胞因子凋亡的需要
DOI：
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发表时间：
1996
影响因子：
15.3
通讯作者：
H. Simon
中科院分区：
文献类型：
--
作者：
S. Yousefi;D. Hoessli;K. Blaser;G. Mills;H. Simon
在变态反应性疾病中，细胞因子白介素5(IL-5)和粒细胞/巨噬细胞集落刺激因子(GM-CSF)表达上调，并被认为通过抑制嗜酸性粒细胞的凋亡而导致血液和组织中的嗜酸性粒细胞增多。在此，我们证明，在新鲜分离的人嗜酸性粒细胞中，IL-3/IL-5/GM-CSF受体β亚基与细胞质酪氨酸激酶相互作用，诱导几种细胞底物的磷酸化，包括β亚基本身。在嗜酸性粒细胞中，Lyn和Syk细胞内酪氨酸激酶与IL-3/IL-5/GM-CSF受体β亚基结合水平较低。用GM-CSF或IL-5刺激后，与IL-3/IL-5/GM-CSF受体β亚基相关的Lyn和Syk的数量迅速而短暂地增加。Lyn是最佳酪氨酸磷酸化和Syk激活所必需的。相反，Syk不是Lyn最佳酪氨酸磷酸化和激活所必需的。这些数据表明，Lyn在传递IL-3、IL-5或GM-CSF信号的酪氨酸激酶级联中位于Syk的近端。与这一模型相一致，Lyn和Syk在人嗜酸粒细胞中通过IL-3/IL-5/GM-CSF受体β亚基诱导的抗凋亡途径(S)的激活中都是必不可少的。
In allergic diseases, the cytokines interleukin (IL)5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are upregulated and have been proposed to cause blood and tissue eosinophilia by inhibition of eosinophil apoptosis. We demonstrate herein, in freshly isolated human eosinophils, that the IL-3/IL-5/GM- CSF receptor beta subunit interacts with cytoplasmic tyrosine kinases to induce phosphorylation of several cellular substrates, including the beta subunit itself. The Lyn and Syk intracellular tyrosine kinases constitutively associate at a low level with the IL-3/IL-5/GM-CSF receptor beta subunit in human eosinophils. Stimulation with GM-CSF or IL-5 results in a rapid and transient increase in the amount of Lyn and Syk associated with the IL-3/IL-5/GM-CSF receptor beta subunit. Lyn is required for optimal tyrosine phosphorylation and activation of Syk. In contrast, Syk is not required for optimal tyrosine phosphorylation and activation of Lyn. These data suggest that Lyn is proximal to Syk in a tyrosine kinase cascade that transduces IL-3, IL-5, or GM-CSF signals. Compatible with this model, both Lyn and Syk are essential for the activation of the antiapoptotic pathway(s) induced through the IL-3/IL- 5/GM-CSF receptor beta subunit in human eosinophils.
影响因子：
56.9
作者：
REN, RB;MAYER, BJ;BALTIMORE, D
通讯作者：
BALTIMORE, D
DOI：
10.1073/pnas.91.11.4683
发表时间：
1994-05-24
影响因子：
11.1
作者：
COREY, SJ;BURKHARDT, AL;TWEARDY, DJ
通讯作者：
TWEARDY, DJ