ULK1 phosphorylation activates its kinase activity and leads to the inhibition of mTORC1, via phosphorylation of TSC2 and raptor (Kim et al. 2011). Thr-180 in the activation loop of the catalytic centre of ULK1 is required for ULK1 kinase activity. This is suggested to be an autophosphorylation site, though the existence of an upstream kinase was not ruled out (Bach et al. 2011). A homologous site in yeast Atg1 is similarly required for kinase activity and suggested to be autophosphorylated (Yeh et al. 2010). Ser-1047 at the extreme C-terminal end of mouse ULK1 was proposed to be the main Ulk1 autophosphorylation site (Dorsey et al. 2009); the equivalent residue in human ULK1 is Thr-1046. ULK1-mediated phosphorylations of ATG13, FIP200, and ULK1 itself triggers autophagy (Mizushima et al. 2011).
Larance, M, James, DE, Bach, M, Ramm, G
protein serine/threonine kinase activity of p-AMPK heterotrimer:AMP:p-S317,467,556,638,T575-ULK1:ATG13:RB1CC1:ATG101 [cytosol]
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