AMP-activated protein kinase (AMPK) as therapeutic target

作者：Sarnowska Elzbieta; Balcerak Anna; Olszyna Serementa Marta; Kotlarek Daria; Sarnowski Tomasz J^*; Siedlecki Janusz A

来源：Postepy Higieny i Medycyny Doswiadczalnej, 2013, 67: 750-760.

• AMPK
• LKB1
• mTOR kinase
• metabolizm
• insulin resistance

AMP-activated protein kinase (AMPK) is one of the major energy sensor at both: cellular and whole body level. It exists as heterotrimer containing three subunits: the catalytic alpha subunit, beta and regulatory gamma. AMPK is localized both in the cytoplasm and in the nucleus. It is activated by increasing concentrations of AMP during the energy shortage, causing activation of catabolic pathways and inhibition of energy consuming processes. AMPK activity can be regulated allosterically: by binding AMP to a regulatory gamma subunit, as well as by phosphorylation on Thr172 of the catalytic alpha subunit by other kinases. Activated AMPK can effectively inhibit the mTOR pathway which is hyperactive in many types of cancer. On the other hand AMPK inactivation associates with the type II diabetes, diet-induced obesity, insulin resistance and the development of other metabolic disorders. The AMPK dysfunction is also observed in inflammation. It was discovered during last years that abnormalities in the AMPK function can induce the metabolic reprogramming in cancer cells known as the Warburg effect. Additionally, AMPK is activated during irradiation. Its activation leads to inhibition of growth. On the other hand, active AMPK enables cells to survive in difficult conditions such as hypoxia, or glucose deprivation. Because of its crucial role in maintaining of the energy homeostasis AMPK is an excellent therapeutic target. However, it still remains unknown what is better: to activate or inhibit the AMPK function.

• 出版日期2013-8-5