Identification of UNC119 as a novel activator of SRC-type tyrosine kinases
Identification of UNC119 as a novel activator of SRC-type tyrosine kinases
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DOI：
10.1074/jbc.m208261200
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发表时间：
2003-03-07
影响因子：
4.8
通讯作者：
Alam, R
中科院分区：
文献类型：
--
作者：
Cen, O;Gorska, MM;Alam, R
Lyn 是一种 Src 型酪氨酸激酶，与嗜酸性粒细胞中的白细胞介素 (IL)-5 受体相关。其激活机制尚不清楚。通过酵母双杂交筛选，我们克隆并表征了一种新的信号分子 Unc119，它与 IL-5Ralpha 和 Src 家族酪氨酸激酶相关。 Unc119 通过与 Src 同源 2 和 3 结构域相互作用来诱导这些激酶的催化活性。 IL-5 刺激嗜酸性粒细胞会增加 Unc119 与 Lyn 的关联并诱导其催化活性。 Lyn 对于嗜酸性粒细胞的存活很重要。用 Unc119 转导的嗜酸性粒细胞具有增加的 Lyn 活性，并且在没有 IL-5 的情况下表现出延长的存活时间。抑制 Unc119 会下调嗜酸性粒细胞的存活。据我们所知，Unc119 是 Src 家族酪氨酸激酶的第一个受体相关激活剂。
Lyn, an Src-type tyrosine kinase, is associated with the interleukin (IL)-5 receptor in eosinophils. The mechanism of its activation is unknown. Through yeast two-hybrid screening we have cloned and characterized a new signaling molecule, Unc119, that associates with IL-5Ralpha and Src family tyrosine kinases. Unc119 induces the catalytic activity of these kinases through interaction with Src homology 2 and 3 domains. IL-5 stimulation of eosinophils increases Unc119 association with Lyn and induces its catalytic activity. Lyn is important for eosinophil survival. Eosinophils that are transduced with Unc119 have increased Lyn activity and demonstrate prolonged survival in the absence of IL-5. Inhibition of Unc119 down-regulates eosinophil survival. To our knowledge Unc119 is the first receptor-associated activator of Src family tyrosine kinases.