Abstract |
The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism. While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation. Mutations in the gamma2 and gamma3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart and elevated glycogen in pig muscle, respectively. A putative glycogen binding domain (GBD) has now been identified in the beta subunits. Coexpression of truncated beta subunits lacking the GBD with alpha and gamma subunits yielded complexes that were active and normally regulated. However, coexpression of alpha and gamma with full-length beta caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti- glycogen or anti- glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated beta subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with gamma2 mutations.
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Authors | Emma R Hudson, David A Pan, John James, John M Lucocq, Simon A Hawley, Kevin A Green, Otto Baba, Tatsuo Terashima, D Grahame Hardie |
Journal | Current biology : CB
(Curr Biol)
Vol. 13
Issue 10
Pg. 861-6
(May 13 2003)
ISSN: 0960-9822 [Print] England |
PMID | 12747836
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Multienzyme Complexes
- Protein Subunits
- Recombinant Fusion Proteins
- Glycogen
- Glycogen Synthase
- PRKAG3 protein, human
- Protein Serine-Threonine Kinases
- AMP-Activated Protein Kinases
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Topics |
- AMP-Activated Protein Kinases
- Arrhythmias, Cardiac
(enzymology, genetics, metabolism)
- Cell Line, Tumor
- Glycogen
(metabolism)
- Glycogen Synthase
(chemistry, metabolism)
- Humans
- Inclusion Bodies
(metabolism, pathology)
- Multienzyme Complexes
(chemistry, genetics, metabolism, ultrastructure)
- Precipitin Tests
- Protein Serine-Threonine Kinases
(chemistry, genetics, metabolism, ultrastructure)
- Protein Structure, Tertiary
- Protein Subunits
- Recombinant Fusion Proteins
(chemistry, genetics, metabolism)
- Sequence Deletion
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