Evidence that the AMP-activated protein kinase stimulates rat liver carnitine palmitoyltransferase I by phosphorylating cytoskeletal components.
The activity of hepatic carnitine palmitoyltransferase I (CPT-I) may be modulated by interactions with cytoskeletal components [Velasco et al. (1998) J. Biol. Chem. 273, 21497-21504]. We have studied whether the AMP-activated protein kinase (AMPK) is involved in this process. AMPK stimulated CPT-I in permeabilized hepatocytes but not in isolated liver mitochondria. In addition, AMPK abrogated the inhibition of CPT-I of isolated mitochondria induced by a cytoskeletal fraction. These two effects of AMPK were not evident when the kinase was inactivated by pretreatment with protein phosphatase 2C. Cytokeratins 8 and 18 were phosphorylated by AMPK in vitro and by incubation of intact hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside, a cell-permeable activator of AMPK. These results provide the first evidence that AMPK stimulates CPT-I by direct phosphorylation of cytoskeletal components.
Velasco
G
G
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
Gómez del Pulgar
T
T
Carling
D
D
Guzmán
M
M
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism* / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007633:Keratins / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology
D009097:Multienzyme Complexes; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008316:Malonyl Coenzyme A; D007633:Keratins; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide