Reactome | Active MTORC1 binds the ULK1 complex

Active MTORC1 binds the ULK1 complex

Stable Identifier

R-HSA-5672817

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, endosome membrane

ReviewStatus

5/5

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Under nutrient-rich conditions, the mTORC1 complex associates with the ULK complex (Mizushima 2010). Binding is mediated by Raptor, a substrate recognition subunit of mTORC1, and the PS domain of ULK1 (Hosokawa et al. 2009).

Active mTORC1 phosphorylates ULK1 Ser-758, which disrupts the interaction between ULK1 and AMPK, thereby maintaining ULK1 in an inactive state (Jung et al. 2009, Kim et al. 2011, Egan et al. 2011).

When cellular energy is depleted, AMPK is activated. It inhibits mTORC1 kinase activity via phosphorylation of both TSC2 and raptor (Gwinn et al. 2008). Inhibition of mTORC1 reduces S758 phosphorylation on ULK1 (Shang et al. 2011). The S758-unphosphorylated ULK1 is able to associate with, and be activated by, AMPK.

Literature References

PubMed ID	Title	Journal	Year
19211835	Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy Natsume, T, Yamada, N, Mizushima, N, Hosokawa, N, Guan, JL, Iemura, S, Miura, Y, Hara, T, Kishi, C, Takehana, K, Takamura, A, Kaizuka, T, Oshiro, N	Mol. Biol. Cell	2009