title: Study of ULK1 Catalytic Activity and Its Regulation.
abstract: During the last decade, the molecular mechanisms controlling the initiation of (macro-)autophagy have been extensively studied. Two macromolecular kinase complexes are central for the initiation of autophagy: the protein kinase unc-51-like kinase 1 (ULK1) complex and the lipid kinase VPS34/Beclin 1 complex. The serine/threonine kinase ULK1 represents the mammalian ortholog of yeast autophagy-related (Atg) protein 1 (Atg1). ULK1 is regulated by upstream nutrient- and energy-sensing kinases, and transmits these signals to the core autophagic machinery. To date, the analysis of ULK1 activation and/or activity is an effective tool to investigate autophagy pathways. As described in this chapter, this can be performed by immunoblotting with phosphosite-specific antibodies against ULK1 and/or ULK1 substrates, by mass spectrometry, or by in vitro kinase assays. Furthermore, the recent design and development of ULK1-specific inhibitors established this kinase as an attractive therapeutic target in settings, where the inhibition of autophagy is desired.
authors.affiliation: Institute of Molecular Medicine I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany. Electronic address: bjoern.stork@uni-duesseldorf.de.
authors.forename: B
authors.initials: B
authors.lastname: Stork
authors.affiliation: University of Freiburg, Freiburg, Germany. Electronic address: joern.dengjel@unifr.ch.
authors.forename: J
authors.initials: J
authors.lastname: Dengjel
mesh_terms: D000818:Animals; D000071189:Autophagy-Related Protein-1 Homolog / Q000032:analysis / Q000378:metabolism*; D015151:Immunoblotting / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012694:Serine; D000071189:Autophagy-Related Protein-1 Homolog; C484754:ULK1 protein, human; C112444:Ulk1 protein, mouse
keywords: ATG101; ATG13; Autophagy; RB1CC1; ULK1