Cell Cycle. 2011 May 1;10(9):1337-8. doi: 10.4161/cc.10.9.15291. Epub 2011 Mar 15.
The serine/threonine kinase ULK1 is a mammalian homolog of AT G1, an upstream component of the core autophagy machinery. Studies in yeast AT G1 kinase complex demonstrate that the AT G1 kinase complex assembly is regulated by phosphorylaltion of AT G13 in a TORC1-dependent manner. However, the mammalian ULK1 complex appears to have different mechanisms of regulation because the mammalian ULK1-AT G13 association is not regulated by TORC1. Recently, we and Shaw’s group reported that AMPK phosphorylates ULK1 in response to cellular energy starvation to control ULK1 kinase function and autophagy induction. When nutrients are sufficient, mTORC1 phosphorylates ULK1, preventing its association and activation by AMPK. These studies have revealed a molecular mechanism of ULK1 regulation by nutrient signals via the coordinated actions of AMPK and mTORC1.
丝氨酸/苏氨酸激酶 ULK1 是哺乳动物中 ATG1 的同源物，ATG1 是核心自噬机制的上游组成部分。酵母 ATG1 激酶复合物的研究表明，ATG1 激酶复合物的组装受到 TORC1 依赖性的 ATG13 磷酸化的调节。然而，哺乳动物的 ULK1 复合物似乎具有不同的调节机制，因为哺乳动物的 ULK1-ATG13 结合不受 TORC1 的调节。最近，我们和 Shaw 小组报道 AMPK 会在细胞能量饥饿时磷酸化 ULK1，以控制 ULK1 激酶功能和自噬的诱导。当营养物质充足时，mTORC1 会磷酸化 ULK1，阻止其与 AMPK 的结合和激活。这些研究揭示了营养信号通过 AMPK 和 mTORC1 的协调作用对 ULK1 进行调控的分子机制。
