LTK is an ER-resident receptor tyrosine kinase that regulates secretion
LTK is an ER-resident receptor tyrosine kinase that regulates secretion
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DOI：
10.1083/jcb.201903068
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发表时间：
2019-08-01
影响因子：
7.8
通讯作者：
Farhan, Hesso
中科院分区：
文献类型：
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作者：
Centonze, Federica G.;Reiterer, Veronika;Farhan, Hesso
内质网 (ER) 是细胞蛋白质稳态的关键调节因子，因为它控制分泌蛋白的折叠、分类和降解。关于环境触发的信号通路如何调节内质网功能已经了解很多，但对内质网的局部信号传导知之甚少。内质网驻留信号分子的鉴定将有助于更深入地了解内质网功能的调节，从而了解蛋白质稳态。在这里，我们证明白细胞酪氨酸激酶（LTK）是一种内质网驻留受体酪氨酸激酶。 LTK 的耗尽及其药理抑制会减少 ER 出口位点的数量并减慢 ER 到高尔基体的转运。此外，我们还发现 LTK 与 Sec12 相互作用并使其磷酸化。 Sec12 磷酸消融突变体的表达会降低 ER 输出效率。因此，LTK-to-Sec12 信号传导代表了具有调节蛋白质稳态潜力的 ER 驻留信号传导模块的第一个例子。
The endoplasmic reticulum (ER) is a key regulator of cellular proteostasis because it controls folding, sorting, and degradation of secretory proteins. Much has been learned about how environmentally triggered signaling pathways regulate ER function, but only little is known about local signaling at the ER. The identification of ER-resident signaling molecules will help gain a deeper understanding of the regulation of ER function and thus of proteostasis. Here, we show that leukocyte tyrosine kinase (LTK) is an ER-resident receptor tyrosine kinase. Depletion of LTK as well as its pharmacologic inhibition reduces the number of ER exit sites and slows ER-to-Golgi transport. Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module with the potential to regulate proteostasis.