Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, TX, USA.
Autophagy. 2011 Aug;7(8):924-6. doi: 10.4161/auto.7.8.15860. Epub 2011 Aug 1.
Ulk1 is a serine/threonine kinase and the mammalian functional homolog of yeast Atg1. It acts at the initiation step of autophagy and forms a complex with mAtg13, FIP200 and Atg101. Assembly of this complex is independent of mTOR signaling, indicating the regulation of autophagy initiation in mammals is different from that in yeast. In a recent study, we reported that Ulk1 can be phosphorylated by mTOR and AMPK kinases. AMPK associates with Ulk1 in nutrient-dependent manner. Rapid dissociation between Ulk1 and AMPK primes cells for fast autophagy induction upon nutrient withdrawal. These studies show that both mTOR and AMPK directly regulate Ulk1 and coordinate the mammalian autophagy initiation.
Ulk1 是一种丝氨酸/苏氨酸激酶，也是酵母 Atg1 的哺乳动物功能同源物。它在自噬的起始步骤中起作用，并与 mAtg13、FIP200 和 Atg101 形成复合物。该复合物的组装不依赖于 mTOR 信号，表明哺乳动物中自噬起始的调节与酵母不同。在最近的一项研究中，我们报告说 Ulk1 可以被 mTOR 和 AMPK 激酶磷酸化。AMPK 以营养依赖的方式与 Ulk1 结合。Ulk1 和 AMPK 之间的快速解离使细胞在营养物质耗尽时快速诱导自噬。这些研究表明，mTOR 和 AMPK 都可以直接调节 Ulk1，并协调哺乳动物自噬的起始。
