AMPKα2 translocates into the nucleus and interacts with hnRNP H: Implications in metformin-mediated glucose uptake

Nami Kim, Jung Ok Lee, Hye Jeong Lee, Soo Kyung Lee, Ji Wook Moon, Su Jin Kim, Sun Hwa Park, Hyeon Soo Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 AMPKα2 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 AMPKα2 phosphorylation-defective mutant did not translocate into the nucleus. Knockdown of AMPKα2 suppressed the differentiation-induced expression of myogenin, a differentiation marker. A physiological AMPK activator, metformin, also induced the translocation of AMPKα2 into the nucleus. Both inhibition and knockdown of AMPKα2 suppressed metformin-mediated glucose uptake. In addition, AMPKα2 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 AMPKα2 and hnRNP H in the nucleus. Knockdown of hnRNP H blocked metformin-induced glucose uptake. In summary, these results demonstrate that AMPKα2 translocates into the nucleus via phosphorylation, AMPKα2 interacts with and phosphorylates hnRNP H in the nucleus, and such a protein-protein interaction modulates metformin-mediated glucose uptake.

Original languageEnglish
Pages (from-to)1800-1806
Number of pages7
JournalCellular Signalling
Volume26
Issue number9
DOIs
Publication statusPublished - 2014 Sep

Keywords

  • AMPK
  • Glucose uptake
  • HnRNP H
  • Phosphorylation
  • Translocation

ASJC Scopus subject areas

  • Cell Biology

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