Reactome | Active MTORC1 phosphorylates ULK1

Active MTORC1 phosphorylates ULK1

Stable Identifier

R-HSA-5672010

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal membrane

ReviewStatus

5/5

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Under nutrient-rich conditions, mTORC1 phosphorylates ULK1 on S758 (Kim et al. 2011, Egan et al. 2011). ULK1 phosphorylation correlates with autophagy inhibition and reduced ULK1 kinase activity (Jung et al. 2009, Ganley et al. 2009, Hosakawa et al. 2009). RB1CC1 (FIP200) is probably phosphorylated (Mizushima 2010). ULK1 phosphorylation on S758 disrupts interaction between ULK1 and AMPK, thereby preventing AMPK from phosphorylating ULK1 at activating sites (Jung et al. 2009, Kim et al. 2011, Egan et al. 2011). If phosphorylation of ULK1 complex components suppresses autophagy, activation might be expected to involve more than suppression of kinases such as mTORC1. The phosphatase inhibitor okadaic acid inhibits autophagy (Blankson et al. 1995) but the protein phosphatase(s) involved in ULK1 dephosphorylation are currently unknown (Wong et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
21258367	AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 Kim, J, Kundu, M, Viollet, B, Guan, KL	Nat. Cell Biol.	2011
21460621	The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR Egan, D, Kim, J, Shaw, RJ, Guan, KL	Autophagy	2011