ArticlePloS one2011
Developmental enhancement of adenylate kinase-AMPK metabolic signaling axis supports stem cell cardiac differentiation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Trial
- Creatine kinase B, a downstream effector of c-Myb, controls migration of osteosarcoma cells via regulation of N-cadherin.Cancer cell international · 2025Article
- AK2-Deficient Mice Recapitulate Impaired Lymphopoiesis of Reticular Dysgenesis Patients, but Also Lack Erythropoiesis.European journal of immunology · 2025Article
- The role of the adenylate kinase 5 gene in various diseases and cancer.Journal of clinical and translational science · 2024Review
- Discovery of Hepatotoxic Equivalent Markers and Mechanism ofMolecules (Basel, Switzerland) · 2022Article
- Maternal exercise improves epithelial development of fetal intestine by enhancing apelin signaling and oxidative metabolism.American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- Comparative Transcriptomic Analysis of mRNAs, miRNAs and lncRNAs in theBiomolecules · 2022Article
- Adenylate Kinase 4-A Key Regulator of Proliferation and Metabolic Shift in Human Pulmonary Arterial Smooth Muscle Cells via Akt and HIF-1α Signaling Pathways.International journal of molecular sciences · 2021Article
- Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies.International journal of molecular sciences · 2021Article
- Adenylate kinase AK2 isoform integral in embryo and adult heart homeostasis.Biochemical and biophysical research communications · 2021Article
- Overexpression of Phosphoribosyl Pyrophosphate Synthase Enhances Resistance ofFrontiers in plant science · 2021Article
- AMPKβ1 and AMPKβ2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification.The Journal of biological chemistry · 2020Article
- Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis.Cell reports · 2020Article
- Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import.The EMBO journal · 2020Article
- Long non-coding RNA BANCR promotes interferon-β-induced cardiomyocyte apoptosis by targeting signal transducer and activator of transcription 1International journal of clinical and experimental pathology · 2020Article
- Adenylate Kinase and Metabolic Signaling in Cancer Cells.Frontiers in oncology · 2020Review
- Article
- Intracellular Energy-Transfer Networks and High-Resolution Respirometry: A Convenient Approach for Studying Their Function.International journal of molecular sciences · 2018Review
- Article
- Inorganic polyphosphate induces accelerated tube formation of HUVEC endothelial cells.Cellular and molecular life sciences : CMLS · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEnergetic and metabolic circuits that orchestrate cell differentiation are largely unknown. Adenylate kinase (AK) and associated AMP-activated protein kinase (AMPK) constitute a major metabolic signaling axis, yet the role of this system in guiding differentiation and lineage specification remains undefined. METHODS AND
resultsCardiac stem cell differentiation is the earliest event in organogenesis, and a suitable model of developmental bioenergetics. Molecular profiling of embryonic stem cells during cardiogenesis revealed here a distinct expression pattern of adenylate kinase and AMPK genes that encode the AK-AMP-AMPK metabolic surveillance axis. Cardiac differentiation upregulated cytosolic AK1 isoform, doubled AMP-generating adenylate kinase activity, and increased AMP/ATP ratio. At cell cycle initiation, AK1 translocated into the nucleus and associated with centromeres during energy-consuming metaphase. Concomitantly, the cardiac AMP-signal receptor AMPKα2 was upregulated and redistributed to the nuclear compartment as signaling-competent phosphorylated p-AMPKα(Thr172). The cardiogenic growth factor TGF-β promoted AK1 expression, while knockdown of AK1, AK2 and AK5 activities with siRNA or suppression by hyperglycemia disrupted cardiogenesis compromising mitochondrial and myofibrillar network formation and contractile performance. Induction of creatine kinase, the alternate phosphotransfer pathway, compensated for adenylate kinase-dependent energetic deficits.
conclusionsDevelopmental deployment and upregulation of the adenylate kinase/AMPK tandem provides a nucleocytosolic energetic and metabolic signaling vector integral to execution of stem cell cardiac differentiation. Targeted redistribution of the adenylate kinase-AMPK circuit associated with cell cycle and asymmetric cell division uncovers a regulator for cardiogenesis and heart tissue regeneration.
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