Active mTORC1 phosphorylates ULK1

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R-HSA-5672010
Type
Reaction [transition]
Species
Homo sapiens
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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
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
21258367 AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

Kim, J, Kundu, M, Viollet, B, Guan, KL

Nat. Cell Biol. 2011
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Catalyst Activity
Title
protein serine/threonine kinase activity of mTORC1:RHEB:GTP:ULK1:ATG13:RB1CC1:ATG101 [lysosomal membrane]
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