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Beschreibung

Serine/threonine-protein kinase ULK1 (UniProt: O70405, also known as EC:2.7.11.1, Serine/threonine-protein kinase Unc51.1, Unc-51-like kinase 1) is encoded by the Ulk1 gene (Gene ID: 22241) in murine species. ULK-1 is a cytosolic serine/threonine protein kinase that is localized in cytosol and preautophagosomal structures. Under condition of starvation, it is localized to punctate structures primarily representing the isolation membrane that sequesters a portion of the cytoplasm resulting in the formation of an autophagosome. Its protein kinase domain is localized to amino acids 16-278. It is involved in autophagy in response to starvation and acts upstream of PI3-kinase (PIK3C3) to regulate the formation of autophagophores, the precursors of autophagosomes. It acts both as a downstream effector and a negative regulator of mTORC1 via interaction with Raptor. ULK1 contains multiple phosphorylation sites, and their phosphorylation status is reported to regulate canonical autophagy. Under unstimulated conditions, it is phosphorylated at serine 637 and 757 by mTOR complex that leads to its inactivation. ULK1 is activated via phosphorylation by AMPK and also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. Despite its similarity with ULK2 in its enzymatic domain, there are major differences in their autophagy-related interactors and their post-translational and transcriptional regulators. ULK1 undergoes phosphorylation at serine 746 by receptor interacting protein kinase 3 (RIPK3) during genotoxic stress-induced alternative autophagy and this phosphorylated form is shown to localize exclusively on the Golgi and is essential for alternative autophagy, but not canonical autophagy. (Ref.: Torii, S., et al. (2020). Nat. Commun. 11: 1754).