title: AMPKα2 translocates into the nucleus and interacts with hnRNP H: implications in metformin-mediated glucose uptake.
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.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: anatomykim@korea.ac.kr.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology; D057900:Transcytosis / Q000187:drug effects*
chemical_list: D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D008687:Metformin; C543928:Prkaa2 protein, rat; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose
keywords: AMPK; Glucose uptake; Phosphorylation; Translocation; hnRNP H