ArticleMolecular biology of the cell2010
Identification of a nuclear export signal in the catalytic subunit of AMP-activated protein kinase.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 120 citations in OpenAlex.
- AMPK Therapy-A Little Goes A Long Way.Cells · 2026Review
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- AMPK phosphorylates WIP1 to promote DNA repair and radioresistance in cancer cells.Cell death & disease · 2025Article
- Spatial regulation of AMPK activity under oxidative stress requires LKB1.bioRxiv : the preprint server for biology · 2025Article
- KAT6A acetylation regulates AMPK function and hypertrophic remodeling in the heart.Molecular metabolism · 2025Article
- RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma.NPJ precision oncology · 2025Article
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- B-type Plexins promote the GTPase activity of Ran to affect androgen receptor nuclear translocation in prostate cancer.Cancer gene therapy · 2023Article
- New insights into activation and function of the AMPK.Nature reviews. Molecular cell biology · 2023Review
- Loss of Mature Lamin A/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPKα Activation.Cells · 2022Article
- AMP-activated protein kinase - a journey from 1 to 100 downstream targets.The Biochemical journal · 2022Article
- Compartmentalization, a key mechanism controlling the multitasking role of the SnRK1 complex.Journal of experimental botany · 2022Review
- AMPK signaling and its targeting in cancer progression and treatment.Seminars in cancer biology · 2022Review
- Article
- Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter.Nature communications · 2022Article
- Mechanical force application to the nucleus regulates nucleocytoplasmic transport.Nature cell biology · 2022Article
- Caspase cleavage and nuclear retention of the energy sensor AMPK-α1 during apoptosis.Cell reports · 2022Article
- Parallel import mechanisms ensure the robust nuclear localization of actin inFrontiers in molecular biosciences · 2022Article
- AMPK Localization: A Key to Differential Energy Regulation.International journal of molecular sciences · 2021Review
- AMPK: restoring metabolic homeostasis over space and time.Molecular cell · 2021Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The metabolic regulator AMP-activated protein kinase (AMPK) maintains cellular homeostasis through regulation of proteins involved in energy-producing and -consuming pathways. Although AMPK phosphorylation targets include cytoplasmic and nuclear proteins, the precise mechanisms that regulate AMPK localization, and thus its access to these substrates, are unclear. We identify highly conserved carboxy-terminal hydrophobic amino acids that function as a leptomycin B-sensitive, CRM1-dependent nuclear export sequence (NES) in the AMPK catalytic subunit (AMPKα). When this sequence is modified AMPKα shows increased nuclear localization via a Ran-dependent import pathway. Cytoplasmic localization can be restored by substituting well-defined snurportin-1 or protein kinase A inhibitor (PKIA) CRM1-binding NESs into AMPKα. We demonstrate a functional requirement in vivo for the AMPKα carboxy-terminal NES, as transgenic Drosophila expressing AMPKα lacking this NES fail to rescue lethality of AMPKα null mutant flies and show decreased activation loop phosphorylation under heat-shock stress. Sequestered to the nucleus, this truncated protein shows highly reduced phosphorylation at the key Thr172 activation residue, suggesting that AMPK activation predominantly occurs in the cytoplasm under unstressed conditions. Thus, modulation of CRM1-mediated export of AMPKα via its C-terminal NES provides an additional mechanism for cells to use in the regulation of AMPK activity and localization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.