Journal
CELLULAR SIGNALLING
Volume 26, Issue 9, Pages 1800-1806Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2014.03.023
Keywords
AMPK; Glucose uptake; hnRNP H; Phosphorylation; Translocation
Categories
Funding
- National Research Foundation of Korea - Korea government [NRF-2013R1A2A2A05004796]
- Kil Chung Hee Fellowship Fund
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Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cytoplasmic protein that plays a critical role in the maintenance of energy homeostasis. However, its role in the nucleus is still largely unknown. Here, we showed that AMPK alpha 2 translocated into the nucleus during muscle differentiation. We also showed that upon treatment with 5-aminoimidazole-4-carboxy-amide-1-D-ribofuranoside (AICAR), an AMPK activator, AMPK rapidly translocated into the nucleus in rat myoblast L6 cells. On the other hand, the AMPK alpha 2 phosphorylation-defective mutant did not translocate into the nucleus. Knockdown of AMPK alpha 2 suppressed the differentiation-induced expression of myogenin, a differentiation marker. A physiological AMPK activator, metformin, also induced the translocation of AMPK alpha 2 into the nucleus. Both inhibition and knockdown of AMPK alpha 2 suppressed metformin-mediated glucose uptake. In addition, AMPK alpha 2 was shown to directly interact with the heterogeneous nuclear ribonucleoprotein H (hnRNP H). AICAR treatment increased the phosphorylation of hnRNP H. Metformin increased the interaction between AMPK alpha 2 and hnRNP H in the nucleus. Knockdown of hnRNP H blocked metformin-induced glucose uptake. In summary, these results demonstrate that AMPK alpha 2 translocates into the nucleus via phosphorylation, AMPK alpha 2 interacts with and phosphorylates hnRNP H in the nucleus, and such a protein-protein interaction modulates metformin-mediated glucose uptake. (C) 2014 Elsevier Inc. All rights reserved.
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