AMP-activated protein kinase (AMPK) is a central regulator of cellular energy homeostasis, playing critical roles in regulating growth and reprogramming metabolism as well as in cellular processes including autophagy and cell polarity. The kinase is activated in response to stresses that deplete ATP supplies such as low glucose, hypoxia, ischemia, and heat shock. In response to low ATP levels, AMPK activation promotes signaling pathways that generate more ATP, including fatty acid oxidation and autophagy, and inhibits anabolic ATP-consuming processes including gluconeogenesis, lipid and protein synthesis. When nutrients are scarce, AMPK also acts as a metabolic checkpoint inhibiting cellular growth. AMPK activation works through direct phosphorylation of multiple enzymes directly involved in these processes as well as through transcriptional control of metabolism by phosphorylating transcription factors, co-activators, and co-repressors. Because of its role in regulating energy homeostasis, AMPK is considered a potential target in the development of new treatments for obesity, type 2 diabetes, the metabolic syndrome, and cancer.
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