Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 18, Pages 11715-11728Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.633271
Keywords
-
Categories
Funding
- Netherlands Organization for Scientific Research (NWO) [864.10.007]
- Swiss National Science Foundation [3100A-0114137]
- EU [LSHM-CT-2004-005272]
- Marie Curie fellowship [PIIF-GA-2012-332230]
- [ETHIIRA 36/05-3]
- [32/05-3]
Ask authors/readers for more resources
The mammalian AMP-activated protein kinase (AMPK) is an obligatory alpha beta gamma heterotrimeric complex carrying a carbohydrate-binding module (CBM) in the beta-subunit (AMPK beta) capable of attaching AMPK to glycogen. Nonetheless, AMPK localizes at many different cellular compartments, implying the existence of mechanisms that prevent AMPK from glycogen binding. Cell-free carbohydrate binding assays revealed that AMPK autophosphorylation abolished its carbohydrate-binding capacity. X-ray structural data of the CBM displays the central positioning of threonine 148 within the binding pocket. Substitution of Thr-148 for a phospho-mimicking aspartate (T148D) prevents AMPK from binding to carbohydrate. Overexpression of isolated CBM or beta 1-containing AMPK in cellular models revealed that wild type( WT) localizes to glycogen particles, whereas T148D shows a diffuse pattern. Pharmacological AMPK activation and glycogen degradation by glucose deprivation but not forskolin enhanced cellular Thr-148 phosphorylation. Cellular glycogen content was higher if pharmacological AMPK activation was combined with overexpression of T148D mutant relative to WT AMPK. In summary, these data show that glycogen-binding capacity of AMPK beta is regulated by Thr-148 autophosphorylation with likely implications in the regulation of glycogen turnover. The findings further raise the possibility of regulated carbohydrate-binding function in a wider variety of CBM-containing proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available