biostudies-literatureMercer TJFrancis Crick InstituteEuropean Research CouncilVersus ArthritisThe Francis Crick InstituteWellcome Trust4491-4493https://www.ebi.ac.uk/biostudies/studies/S-EPMC8726633biostudies-literatureUnknown17(12)The mammalian ULK kinase complex is the most upstream component in the macroautophagy/autophagy signaling pathway. ULK1 and homolog ULK2, the sole serine/threonine kinases in autophagy, transduce an array of autophagy-inducing stimuli to downstream autophagic machinery, regulating autophagy from autophagosome initiation to fusion of autophagosomes with lysosomes. ULK signaling is also implicated in a diverse array of non-canonical processes from necroptosis to ER-Golgi trafficking to stress granule clearance. However, the exact mechanisms by which ULK regulates these diverse processes remain largely unknown. Most notably, the number of validated ULK substrates is surprisingly low. Our study identifies new ULK substrates from a wide array of protein families and signaling pathways and suppoAutophagyThe ingenious ULKs: expanding the repertoire of the ULK complex with phosphoproteomics.PMC8726633GA 78850810187FC001187788508Mercer TJTooze SAfalseThe ingenious ULKs: expanding the repertoire of the ULK complex with phosphoproteomics.The mammalian ULK kinase complex is the most upstream component in the macroautophagy/autophagy signaling pathway. ULK1 and homolog ULK2, the sole serine/threonine kinases in autophagy, transduce an array of autophagy-inducing stimuli to downstream autophagic machinery, regulating autophagy from autophagosome initiation to fusion of autophagosomes with lysosomes. ULK signaling is also implicated in a diverse array of non-canonical processes from necroptosis to ER-Golgi trafficking to stress granule clearance. However, the exact mechanisms by which ULK regulates these diverse processes remain largely unknown. Most notably, the number of validated ULK substrates is surprisingly low. Our study identifies new ULK substrates from a wide array of protein families and signaling pathways and suppo2021-01-01T00:00:00Z2021 Dec2025-04-19T10:10:22.162Z2022-02-11T14:47:43.001ZS-EPMC87266333452032910.1080/15548627.2021.1968615