Hepatic amino acid‐dependent signaling is under the control of AMP‐dependent protein kinase

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Abstract
It has become increasingly clear in recent years that amino acids can stimulate a signal transduction pathway resulting in the phosphorylation of mammalian target of rapamycin downstream targets. We have now found that amino acid‐dependent phosphorylation of p70S6 kinase and of S6 in hepatocytes is prevented when AMP‐dependent protein kinase (AMPK) is activated by either the purine ribonucleoside analogue AICAriboside, fructose or glycerol. Insulin‐dependent phosphorylation of protein kinase B is not affected by AMPK activation. Protein synthesis is strongly inhibited when AMPK is activated. It is concluded that amino acid‐dependent signaling, a protein‐anabolic signal, can be effectively antagonized by activation of AMPK.