Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jul;7(7):696-706.
doi: 10.4161/auto.7.7.15451. Epub 2011 Jul 1.

Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop

Antje S Löffler  1 , Sebastian Alers, Alexandra M Dieterle, Hildegard Keppeler, Mirita Franz-Wachtel, Mondira Kundu, David G Campbell, Sebastian Wesselborg, Dario R Alessi, Björn Stork
Affiliations

Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop

Antje S Löffler et al. Autophagy. 2011 Jul.

Abstract

Unc-51-like kinase 1 (Ulk1) plays a central role in autophagy induction. It forms a stable complex with Atg13 and focal adhesion kinase (FAK) family interacting protein of 200 kDa (FIP 200). This complex is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1) in a nutrient-dependent way. AMP-activated protein kinase (AMPK), which is activated by LKB1/Strad/Mo25 upon high AMP levels, stimulates autophagy by inhibiting mTORC1. Recently, it has been described that AMPK and Ulk1 interact and that the latter is phosphorylated by AMPK. This phosphorylation leads to the direct activation of Ulk1 by AMPK bypassing mTOR-inhibition. Here we report that Ulk1/2 in turn phosphorylates all three subunits of AMPK and thereby negatively regulates its activity. Thus, we propose that Ulk1 is not only involved in the induction of autophagy, but also in terminating signaling events that trigger autophagy. In our model, phosphorylation of AMPK by Ulk1 represents a negative feedback circuit.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Substances

LinkOut - more resources