ULK1 Recombinant Rabbit mAb (S-5302)

ULK1 (Unc-51-like kinase 1) is a serine/threonine protein kinase that serves as a core regulatory factor in autophagy initiation and plays a critical role in nutrient sensing and cellular homeostasis maintenance. As the mammalian homolog of the ATG1 kinase, ULK1 is the catalytic subunit of the ULK1 complex (comprising ULK1, ATG13, FIP200, and ATG101), which represents the most upstream component of the autophagy signaling pathway. Under nutrient-rich conditions, mTORC1 directly phosphorylates ULK1 at multiple sites (e.g., Ser757), inhibiting its kinase activity and thereby blocking autophagy initiation; conversely, under energy stress or nutrient deprivation, AMPK phosphorylates ULK1 at distinct sites (e.g., Ser317, Ser555) to activate its activity, while also relieving ULK1 from inhibition by suppressing mTORC1. Once activated, ULK1 promotes phagophore formation by phosphorylating downstream substrates (including ATG13, ATG14, Beclin-1, and VPS34 complex components), subsequently initiating autophagosome assembly and maturation. Beyond its classical role in autophagy regulation, ULK1 also participates in non-autophagy biological processes such as endoplasmic reticulum-Golgi trafficking, mitosis, and innate immune responses, regulating interferon responses through phosphorylation of immune modulators like STING. Dysfunction of ULK1 is closely associated with the development and progression of neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease), metabolic disorders, and various cancers, making it an important drug target for these conditions. Particularly in the field of oncology, ULK1 inhibitors are being extensively studied to enhance the sensitivity of chemotherapy and immunotherapy.