2012 March 2 | Maria M. Mihaylova and Reuben J. Shaw
AMP-activated protein kinase (AMPK) is a central regulator of cellular and organismal metabolism, playing critical roles in growth, metabolism, and cellular processes such as autophagy and cell polarity. AMPK is activated when intracellular ATP levels decrease, promoting catabolic pathways to generate more ATP and inhibiting anabolic pathways. It exists as a heterotrimer composed of a catalytic α subunit and regulatory β and γ subunits. AMPK activation can be mediated by nucleotide binding and phosphorylation, with LKB1 being a key upstream kinase. AMPK is involved in regulating the mammalian target of rapamycin complex 1 (mTORC1) and controlling cell growth, and it also regulates autophagy by phosphorylating ULK1. AMPK affects metabolism through transcriptional regulation, targeting transcription factors, coactivators, histone deacetylases, and histones. Additionally, AMPK controls cell polarity and cytoskeletal dynamics, influencing microtubule dynamics and microtubule-associated proteins. The convergence of AMPK signaling with other pathways, such as PI3K and Erk, highlights its role in coordinating cell growth, metabolism, and fate.AMP-activated protein kinase (AMPK) is a central regulator of cellular and organismal metabolism, playing critical roles in growth, metabolism, and cellular processes such as autophagy and cell polarity. AMPK is activated when intracellular ATP levels decrease, promoting catabolic pathways to generate more ATP and inhibiting anabolic pathways. It exists as a heterotrimer composed of a catalytic α subunit and regulatory β and γ subunits. AMPK activation can be mediated by nucleotide binding and phosphorylation, with LKB1 being a key upstream kinase. AMPK is involved in regulating the mammalian target of rapamycin complex 1 (mTORC1) and controlling cell growth, and it also regulates autophagy by phosphorylating ULK1. AMPK affects metabolism through transcriptional regulation, targeting transcription factors, coactivators, histone deacetylases, and histones. Additionally, AMPK controls cell polarity and cytoskeletal dynamics, influencing microtubule dynamics and microtubule-associated proteins. The convergence of AMPK signaling with other pathways, such as PI3K and Erk, highlights its role in coordinating cell growth, metabolism, and fate.