| First Author | Sakoda H | Year | 2005 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 289 |
| Issue | 3 | Pages | E474-81 |
| PubMed ID | 15886229 | Mgi Jnum | J:100920 |
| Mgi Id | MGI:3589995 | Doi | 10.1152/ajpendo.00003.2005 |
| Citation | Sakoda H, et al. (2005) Glycogen debranching enzyme association with beta-subunit regulates AMP-activated protein kinase activity. Am J Physiol Endocrinol Metab 289(3):E474-81 |
| abstractText | AMP-activated protein kinase (AMPK) regulates both glycogen and lipid metabolism functioning as an intracellular energy sensor. In this study, we identified a 160-kDa protein in mouse skeletal muscle lysate by using a glutathione-S-transferase (GST)-AMPK fusion protein pull-down assay. Mass spectrometry and a Mascot search revealed this protein to be a glycogen debranching enzyme (GDE). The association between AMPK and GDE was observed not only in the overexpression system but also endogenously. Next, we showed the beta1-subunit of AMPK to be responsible for the association with GDE. Furthermore, experiments using deletion mutants of the beta1-subunit of AMPK revealed amino acids 68-123 of the beta1-subunit to be sufficient for GDE binding. W100G and K128Q, both beta1-subunit mutants, are reportedly incapable of binding to glycogen, but both bound GDE, indicating that the association between AMPK and GDE does not involve glycogen. Rather, the AMPK-GDE association is likely to be direct. Overexpression of amino acids 68-123 of the beta1-subunit inhibited the association between endogenous AMPK and GDE. Although GDE activity was unaffected, basal phosphorylation and kinase activity of AMPK, as well as phosphorylation of acetyl-CoA carboxylase, were significantly increased. Thus it is likely that the AMPK-GDE association is a novel mechanism regulating AMPK activity and the resultant fatty acid oxidation and glucose uptake. |
