Hepatic amino acid-dependent signaling is under the control of AMP-dependent protein kinase.
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.
Dubbelhuis
Peter F
PF
Department of Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Meijer
Alfred J
AJ
D000596:Amino Acids; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction
D000596:Amino Acids; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; C118888:AMP-dependent kinase (ATP-forming); D017856:Phosphotransferases (Phosphate Group Acceptor)