RGD Reference Report - AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. - Rat Genome Database

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AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling.

Authors: Bolster, DR  Crozier, SJ  Kimball, SR  Jefferson, LS 
Citation: Bolster DR, etal., J Biol Chem 2002 Jul 5;277(27):23977-80.
RGD ID: 727370
Pubmed: PMID:11997383   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.C200171200   (Journal Full-text)

AMP-activated protein kinase (AMPK) is viewed as an energy sensor that acts to modulate glucose uptake and fatty acid oxidation in skeletal muscle. Given that protein synthesis is a high energy-consuming process, it may be transiently depressed during cellular energy stress. Thus, the intent of this investigation was to examine whether AMPK activation modulates the translational control of protein synthesis in skeletal muscle. Injections of 5-aminoimidazole-4-carboxamide 1-beta-d-ribonucleoside (AICAR) were used to activate AMPK in male rats. The activity of alpha1 AMPK remained unchanged in gastrocnemius muscle from AICAR-treated animals compared with controls, whereas alpha2 AMPK activity was significantly increased (51%). AICAR treatment resulted in a reduction in protein synthesis to 45% of the control value. This depression was associated with decreased activation of protein kinases in the mammalian target of rapamycin (mTOR) signal transduction pathway as evidenced by reduced phosphorylation of protein kinase B on Ser(473), mTOR on Ser(2448), ribosomal protein S6 kinase on Thr(389), and eukaryotic initiation factor eIF4E-binding protein on Thr(37). A reduction in eIF4E associated with eIF4G to 10% of the control value was also noted. In contrast, eIF2B activity remained unchanged in response to AICAR treatment and therefore would not appear to contribute to the depression in protein synthesis. This is the first investigation to demonstrate changes in translation initiation and skeletal muscle protein synthesis in response to AMPK activation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of fatty acid oxidation involved_inNAS 727370PMID:11997383UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Prkaa1  (protein kinase AMP-activated catalytic subunit alpha 1)

Objects referenced in this article
Gene Mtor mechanistic target of rapamycin kinase Rattus norvegicus
Gene Prkaa2 protein kinase AMP-activated catalytic subunit alpha 2 Rattus norvegicus

Additional Information