Affinage

PRKAA2

5'-AMP-activated protein kinase catalytic subunit alpha-2 · UniProt P54646

Length
552 aa
Mass
62.3 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKAA2 (AMPKα2) is the catalytic subunit of the AMPK energy-sensing kinase, which couples cellular energy status to a broad transcriptional and post-translational program controlling autophagy, mitochondrial homeostasis, and systemic glucose metabolism (PMID:21258367, PMID:12546688). Sensing of low energy occurs through adenine-nucleotide binding to the γ-subunit, where CBS3 is the high-affinity exchangeable AMP/ADP/ATP site whose nucleotide preference is allosterically tuned by AMP occupancy at CBS4 and which also binds NADPH competitively (PMID:28615457); this AMP-sensing mechanism is exploited pharmacologically by cordycepin monophosphate, which mimics all three effects of AMP and is abolished by a γ-subunit AMP-binding mutation (PMID:31991096). A parallel lysosomal glucose-sensing branch activates AMPK when low fructose-1,6-bisphosphate releases aldolase from v-ATPase, a circuit that can be engaged chemically (aldometanib) or via sirtuin-dependent deacetylation of the v-ATPase V1E1 subunit (PMID:36217034, PMID:39695235), while a calcium branch operates through STIM2-coordinated CaMKK2 signaling (PMID:30335546). Once active, AMPKα2 directly phosphorylates a defined substrate set: ULK1 (Ser317/Ser777) to initiate starvation autophagy in opposition to mTOR (PMID:21258367), raptor to suppress mTORC1 and enforce energy-stress cell-cycle arrest (PMID:18439900), PGC-1α (Thr177/Ser538) to drive mitochondrial and GLUT4 gene expression in muscle (PMID:17609368), and ULK1 (Ser556/Ser694) to restrain NIX-dependent programmed mitophagy while promoting Parkin-dependent damage-induced mitophagy (PMID:39532100). Through its control of autophagic flux, AMPKα2 also governs SQSTM1/p62-mediated clearance of the fission factor DNM1L to maintain mitochondrial morphology (PMID:28085543). Beyond canonical metabolic targets, AMPK phosphorylates OGT to displace it from chromatin and reduce histone H2B O-GlcNAcylation in a reciprocal regulatory loop (PMID:24692660), and suppresses tensin expression to limit β1-integrin activity and fibrillar adhesion (PMID:28289092). Physiologically, Prkaa2 loss produces systemic insulin resistance and hyperglycemia involving autonomic signaling rather than a muscle-intrinsic transport defect (PMID:12546688), and AMPK stability and activity depend on β-subunit glycogen binding (PMID:32610071). The catalytic α-subunit carries its own NLS and CRM1-dependent NES enabling regulated nucleo-cytoplasmic shuttling (PMID:34681581).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 High

    Established the physiological role of AMPKα2 in systemic glucose homeostasis and showed its insulin-resistance phenotype is not muscle-intrinsic, redirecting attention to whole-body neuroendocrine control.

    Evidence AMPKα2 knockout mice with hyperinsulinemic-euglycaemic clamp, isolated muscle transport assays, and catecholamine measurement

    PMID:12546688

    Open questions at the time
    • Does not identify the AMPKα2 substrates mediating autonomic effects
    • Tissue source of systemic insulin resistance not pinpointed
  2. 2007 High

    Defined a direct transcriptional output of AMPK by showing it phosphorylates PGC-1α to drive mitochondrial biogenesis gene programs.

    Evidence In vitro kinase assay, mutagenesis, and PGC-1α-knockout primary muscle cells with promoter reporter

    PMID:17609368

    Open questions at the time
    • Relative contribution of α2 vs α1 not isolated
    • Downstream coactivator partners on the promoter not mapped
  3. 2008 High

    Connected AMPK to mTORC1 inhibition by identifying raptor as a direct substrate whose phosphorylation recruits 14-3-3 and enforces energy-stress cell-cycle arrest.

    Evidence Proteomic substrate identification, in vitro kinase assay, Co-IP, mutagenesis, and genetic epistasis

    PMID:18439900

    Open questions at the time
    • Quantitative balance between raptor and other mTORC1 inputs unresolved
    • α-isoform specificity not addressed
  4. 2011 High

    Resolved how AMPK initiates autophagy, showing direct ULK1 phosphorylation and reciprocal mTOR-mediated disruption of the AMPK-ULK1 interaction under nutrient sufficiency.

    Evidence In vitro phosphorylation, mutagenesis, Co-IP, and genetic knockout cells

    PMID:21258367

    Open questions at the time
    • Does not separate α1 from α2 catalytic contribution
    • In vivo relevance of specific sites in tissues not tested here
  5. 2014 High

    Extended AMPK function to chromatin regulation by showing it phosphorylates OGT to block chromatin association and reduce histone O-GlcNAcylation, with reciprocal OGT regulation of AMPK.

    Evidence In vitro kinase assay, Co-IP, ChIP, mutagenesis, and transcription reporter

    PMID:24692660

    Open questions at the time
    • Genome-wide scope of affected loci not defined
    • Physiological contexts where the feedback loop dominates unclear
  6. 2015 High

    Revealed how cancer cells suppress AMPK by identifying MAGE-A3/6-TRIM28 as a ubiquitin ligase that degrades the catalytic α-subunit, inhibiting autophagy and activating mTOR.

    Evidence Substrate screen, Co-IP, ubiquitination assay, and gain/loss-of-function with viability readouts (demonstrated for α1)

    PMID:25679763

    Open questions at the time
    • Direct demonstration on the α2 isoform not shown
    • Degron residues on AMPKα not mapped
  7. 2016 Medium

    Linked AMPK to lineage and lipid-handling transcriptional programs, including osteogenesis/adipogenesis via Gfi1-OPN, macrophage cholesterol efflux via LXRα-ABCA1, and antiviral restriction of HBV through autolysosomal degradation.

    Evidence Reporter assays, ChIP, siRNA silencing, ectopic bone formation, and HBV infection autophagy-flux models

    PMID:27283242 PMID:27305174 PMID:27343431

    Open questions at the time
    • AMPKα2-specific requirement not isolated from α1
    • Direct kinase substrates in each pathway not identified
    • Single-lab observations per pathway
  8. 2017 High

    Mapped the nucleotide-sensing core, establishing CBS3 as the high-affinity exchangeable site with CBS4-driven allostery, and dissected AMPK's roles in mitochondrial fission control, integrin/adhesion regulation, and macrophage inflammation.

    Evidence HDX-MS and competition binding (CBS3); Prkaa1/2 KO mice with SQSTM1-DNM1L Co-IP; tensin loss/rescue with traction microscopy; myeloid-specific KO sepsis model with PKM2 rescue

    PMID:28085543 PMID:28289092 PMID:28615457 PMID:29109024

    Open questions at the time
    • CBS3 nucleotide work uses reconstituted complexes, not in-cell occupancy
    • Direct kinase substrates for tensin and PKM2 effects not defined
  9. 2018 High

    Distinguished AMPK's energy and calcium activation inputs and excluded direct ROS oxidation, showing STIM2 regulates the calcium/CaMKK2 axis while mitochondrial ROS act indirectly via ATP/ADP changes.

    Evidence Reciprocal Co-IP and colocalization with STIM2; Cys→Ala mutagenesis with mitochondria-targeted ROS generators and ATP/ADP measurement

    PMID:30232152 PMID:30335546

    Open questions at the time
    • STIM2 finding is single-lab, Medium confidence
    • Molecular mechanism of STIM2-AMPK colocalization not resolved
  10. 2020 High

    Defined determinants of AMPK pharmacology and stability, validating AMP-mimicry by cordycepin monophosphate via the γ-subunit and establishing β-subunit glycogen binding as required for AMPK protein stability and activity in muscle.

    Evidence Nucleotide quantification, cell-free assays, γ-subunit mutagenesis (cordycepin); β2-W98A knock-in mice with metabolic phenotyping

    PMID:31991096 PMID:32610071

    Open questions at the time
    • Glycogen-binding stabilization mechanism at the molecular level not detailed
    • α2-specific stability dependence not isolated
  11. 2021 Medium

    Synthesized the regulated nucleo-cytoplasmic shuttling of AMPKα2, attributing nuclear import to an NLS on the kinase domain and export to RanGTPase-CRM1 recognition of an α-subunit NES.

    Evidence Review compiling fractionation, NES deletion/mutation, and CRM1-inhibition localization studies

    PMID:34681581

    Open questions at the time
    • Review-level synthesis, not primary experiments
    • Stimulus-specific shuttling kinetics not quantified
  12. 2022 High

    Established a lysosomal glucose-sensing branch upstream of AMPK in which low FBP releases aldolase from v-ATPase to activate the lysosomal AMPK pool, druggable by aldometanib.

    Evidence Chemical screen, biochemical binding assays, lysosomal AMPK activity, and lifespan/metabolic phenotyping across rodents and C. elegans

    PMID:36217034

    Open questions at the time
    • Molecular bridge from v-ATPase to AMPK activation not fully defined
    • α2-specific contribution to lysosomal pool not isolated
  13. 2024 High

    Refined AMPK's mitophagy control by showing it phosphorylates ULK1 (Ser556/Ser694) to restrain NIX-dependent programmed mitophagy while promoting Parkin-dependent damage mitophagy, and uncovered an upstream LCA-TULP3-sirtuin-v-ATPase route to AMPK activation.

    Evidence In vitro kinase assays, mutagenesis, mito-QC and aged-mouse in vivo models, phosphoproteomics; LCA-TULP3 Co-IP with deacetylation assays and cross-species lifespan

    PMID:39532100 PMID:39695235

    Open questions at the time
    • How AMPK switches between restraining and promoting mitophagy contextually not fully resolved
    • Direct AMPK substrate in the Parkin arm not specified
  14. 2024 Medium

    Illustrated drug-induced AMPK dysregulation, showing crizotinib lowers AMPK Ser485/491 phosphorylation to impair autophagosome-lysosome fusion and cardiomyocyte clearance of MET, reversible by metformin.

    Evidence In vitro and in vivo cardiotoxicity models with autophagy-flux assays, phosphorylation analysis, and MET silencing

    PMID:37733896

    Open questions at the time
    • Single-lab Medium-confidence study
    • Whether Ser485/491 change is direct or indirect not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which AMPK functions are specifically executed by the α2 (PRKAA2) catalytic isoform versus α1, since most substrate and phenotype data are reported for AMPKα generically.
  • No isoform-resolved substrate map
  • α2-specific structural and localization determinants incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0140299 molecular sensor activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 2 GO:0005764 lysosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9612973 Autophagy 4 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-162582 Signal Transduction 2
Partners
CAMKK2OGTPPARGC1APRKNRPTORSTIM2TRIM28ULK1
Complex memberships
AMPK heterotrimer

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 AMPK directly phosphorylates ULK1 at Ser317 and Ser777 to activate autophagy under glucose starvation. Under nutrient sufficiency, mTOR phosphorylates ULK1 at Ser757, disrupting the AMPK-ULK1 interaction and preventing ULK1 activation. In vitro phosphorylation assay, mutagenesis, co-immunoprecipitation, genetic knockout cells Nature cell biology High 21258367
2008 AMPK directly phosphorylates raptor (the mTOR binding partner) on two conserved serine residues, inducing 14-3-3 binding to raptor; this phosphorylation is required for mTORC1 inhibition and cell-cycle arrest induced by energy stress. Proteomic/bioinformatic substrate identification, in vitro kinase assay, Co-IP, mutagenesis, genetic epistasis Molecular cell High 18439900
2007 AMPK directly phosphorylates PGC-1alpha at Thr177 and Ser538 both in vitro and in cells; these phosphorylations are required for AMPK-dependent induction of the PGC-1alpha promoter and downstream gene expression (GLUT4, mitochondrial genes) in skeletal muscle. In vitro kinase assay, site-directed mutagenesis, PGC-1alpha-knockout primary muscle cells, reporter assay Proceedings of the National Academy of Sciences of the United States of America High 17609368
2015 The cancer-germline ubiquitin ligase MAGE-A3/6-TRIM28 ubiquitinates and degrades AMPKα1 (PRKAA1), leading to inhibition of autophagy and activation of mTOR signaling; this represents a mechanism by which cancer cells suppress AMPK activity. Substrate screen, Co-IP, ubiquitination assay, genetic gain/loss-of-function, cell viability assay Cell High 25679763
2017 AMPK negatively regulates β1-integrin activity in fibroblasts by suppressing expression of the integrin-binding proteins tensin1 and tensin3; loss of AMPK upregulates tensins, which bind β1-integrins to promote fibrillar adhesion formation, cell spreading, traction stress, and fibronectin fibrillogenesis. Loss-of-function (siRNA/genetic deletion), integrin activity assay, traction force microscopy, tensin rescue/silencing experiments The Journal of cell biology High 28289092
2014 AMPK directly phosphorylates OGT (O-GlcNAc transferase), and while this phosphorylation does not alter OGT enzymatic activity, it inhibits OGT-chromatin association, reducing histone H2B O-GlcNAcylation and gene transcription. Conversely, OGT O-GlcNAcylates AMPK and positively regulates AMPK activity, creating a feedback loop. In vitro kinase assay, Co-IP, chromatin immunoprecipitation, mutagenesis, gene transcription reporter assay Nucleic acids research High 24692660
2018 STIM2 (a calcium sensor) physically interacts with both AMPK and CaMKK2; increased intracellular calcium promotes AMPK colocalization with STIM2, and STIM2 deficiency attenuates calcium-induced but not energy-stress-induced AMPK activation, indicating STIM2 is a regulator of the CaMKK2-AMPK calcium-signaling axis. Co-immunoprecipitation, fluorescence microscopy colocalization, genetic knockdown, selective AMPK activation assays FASEB journal Medium 30335546
2018 Mitochondria-derived ROS activate AMPK indirectly (via effects on mitochondrial ATP production and changes in ATP/ADP ratio) rather than by direct oxidation of redox-sensitive cysteine residues (Cys299/Cys304) on the AMPK α subunit; mutation of these cysteines to alanine did not alter the AMPK response to H2O2. Mutagenesis (Cys→Ala), exogenous H2O2 treatment, mitochondria-targeted ROS generator (MitoParaquat), ATP/ADP ratio measurement, redox-sensitive fluorescent proteins The Journal of biological chemistry High 30232152
2017 Deletion of PRKAA (AMPKα, including the α2 isoform) causes defective autophagy, leading to accumulation of DNM1L (dynamin-1-like) and aberrant mitochondrial fragmentation in vascular endothelial cells; the autophagy receptor SQSTM1/p62 binds DNM1L and directs it to autophagosomes for degradation, linking PRKAA activity to mitochondrial fission control. Genetic knockout (Prkaa1/Prkaa2 KO mice), autophagy inhibition (chloroquine, ATG7 siRNA), autophagy activation (ATG7 overexpression, rapamycin), Co-IP of SQSTM1-DNM1L, isolated aorta contractility assay Autophagy High 28085543
2024 AMPK directly inhibits NIX-dependent (programmed) mitophagy by phosphorylating ULK1 at Ser556 and a newly identified site Ser694, triggering 14-3-3-mediated sequestration of ULK1. Conversely, AMPK enhances depolarization-induced (damage-induced) mitophagy by increasing Parkin phosphorylation, independently of ULK1. In vitro kinase assay, mutagenesis, mito-QC mouse model (in vivo), cell-based mitophagy assays, phosphoproteomic identification of Ser694 Molecular cell High 39532100
2022 Blocking FBP (fructose-1,6-bisphosphate) binding to aldolase with the small molecule aldometanib prevents aldolase from associating with v-ATPase on lysosomes, thereby selectively activating the lysosomal pool of AMPK and mimicking cellular glucose starvation; this demonstrates that aldolase acts as a glucose sensor upstream of lysosomal AMPK. Chemical screen, biochemical binding assays, lysosomal AMPK activity measurement, metabolic phenotyping in rodents, C. elegans and mouse lifespan assays Nature metabolism High 36217034
2024 LCA (lithocholic acid) binds TULP3, which allosterically activates sirtuins; activated sirtuins deacetylate the V1E1 subunit of v-ATPase at residues K52, K99, and K191, which inhibits v-ATPase and activates AMPK through the lysosomal glucose-sensing pathway. Proteomics/Co-IP identifying TULP3 as sirtuin-interacting LCA receptor, in vitro deacetylation assays, mutagenesis (3KR deacetylation mimic), muscle-specific viral expression in aged mice, AMPK activity assays, lifespan assays in C. elegans and flies Nature High 39695235
2020 Cordycepin (3'-deoxyadenosine) is converted intracellularly into cordycepin monophosphate, which mimics all three effects of AMP on AMPK (activation, protection from dephosphorylation, allosteric activation); AMPK activation by cordycepin is blocked by a γ-subunit mutation that prevents AMP binding, confirming the AMP-mimicry mechanism. Nucleotide quantification in intact cells, cell-free AMPK assays, genetic AMPK knockout, γ-subunit mutagenesis Cell chemical biology High 31991096
2017 Deconvolution of AMPK adenine nucleotide binding established that CBS3 (not CBS1) is the high-affinity exchangeable AMP/ADP/ATP-binding site in the γ-subunit; AMP binding at CBS4 increases AMP affinity at CBS3 by ~100-fold and reverses CBS3's AMP/ATP preference. NADPH (in addition to NADH) directly and competitively binds AMPK at the CBS3 site. Quantitative competition binding assays, hydrogen-deuterium exchange mass spectrometry, wild-type and mutant AMPK protein complexes The Journal of biological chemistry High 28615457
2017 AMPK deficiency in myeloid cells increases PKM2-dependent aerobic glycolysis, leading to enhanced HMGB1 release from macrophages/monocytes and promoting sepsis; pharmacological AMPK activation (A-769662) protects against endotoxic shock, while PKM2 inhibition rescues the pro-inflammatory phenotype of AMPKα-deficient mice. Myeloid-specific AMPKα knockout mice, pharmacological activation/inhibition, HMGB1 measurement, polymicrobial sepsis model, glycolysis/lactate assays Brain, behavior, and immunity High 29109024
2003 AMPKα2-deficient (Prkaa2−/−) mice display elevated blood glucose, reduced plasma insulin in the fed state, in vivo insulin resistance, and reduced muscle glycogen synthesis; the insulin resistance was not intrinsic to skeletal muscle (isolated muscle glucose transport was normal), suggesting AMPKα2 regulates systemic glucose homeostasis partly through modulation of the autonomic nervous system (increased catecholamine excretion). Genetic knockout mouse (AMPKα2−/−), hyperinsulinemic-euglycaemic clamp, isolated muscle glucose transport assay, dominant-negative AMPK transgenic muscle mice, catecholamine measurement Biochemical Society transactions High 12546688
2021 AMPKα2 nuclear localization employs a nuclear localization signal (NLS) present on the AMPKα2 kinase domain, while nuclear export involves RanGTPase-CRM1-mediated recognition of a nuclear export sequence (NES) on the α subunit; nucleo-cytoplasmic shuttling is regulated by starvation, exercise, heat shock, oxidants, cell density, and circadian rhythm. Subcellular fractionation, nuclear export sequence deletion/mutation analysis, CRM1 inhibition, fluorescence localization studies (compiled from multiple studies reviewed) International journal of molecular sciences Medium 34681581
2020 AMPK-glycogen binding via the β2 subunit CBM (disrupted by W98A knock-in mutation) is required to stabilize AMPK protein and kinase activity in skeletal muscle; β2-W98A KI mice show reduced total AMPK protein and kinase activity in muscle, increased adiposity, impaired whole-body glucose handling, and reduced maximal exercise capacity. Whole-body knock-in mouse (β2-W98A), systematic metabolic phenotyping, AMPK kinase activity assays, tissue AMPK protein quantification Molecular metabolism High 32610071
2024 Crizotinib inhibits PRKAA/AMPK phosphorylation at Ser485/491, impairing autophagosome-lysosome fusion and preventing MET protein degradation; metformin restores PRKAA (Ser485/491) phosphorylation, re-activates autophagy flux, and rescues crizotinib-induced cardiomyocyte injury. In vitro cardiomyocyte models, in vivo mouse cardiotoxicity model, autophagy flux assay, PRKAA phosphorylation analysis, metformin rescue experiment, MET silencing Autophagy Medium 37733896
2016 PRKAA/AMPK is activated by HBV-induced oxidative stress and restricts HBV production by promoting autolysosome-dependent degradation through stimulation of cellular ATP levels, leading to depletion of autophagic vacuoles that HBV depends on for replication. HBV infection cell model, PRKAA activation/inhibition, autophagy flux assay, ATP measurement, autophagic vacuole quantification Autophagy Medium 27305174
2016 AMPK promotes osteogenesis and inhibits adipogenesis through downregulation of the transcriptional repressor Gfi1, which dissociates from the osteopontin (OPN) promoter upon AMPK activation, resulting in OPN upregulation; overexpression or dominant-negative Gfi1 modulates osteogenesis and adipogenesis accordingly. Lentiviral AMPKα overexpression, Gfi1 overexpression/dominant-negative constructs, luciferase reporter (OPN promoter), ChIP (Gfi1 binding), ectopic bone formation assay Cellular signalling Medium 27283242
2016 AMPK activates LXRα expression in macrophages, which then transcriptionally upregulates ABCA1 via binding to the LXR-responsive element in the ABCA1 promoter, resulting in increased cholesterol efflux; LXRβ silencing did not affect this pathway, establishing LXRα specificity. Pharmacological and genetic AMPK activation/knockdown, luciferase reporter assay, chromatin immunoprecipitation (ChIP), LXRα/β siRNA silencing, cholesterol efflux assay The international journal of biochemistry & cell biology Medium 27343431

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology 5964 21258367
2017 AMPK: guardian of metabolism and mitochondrial homeostasis. Nature reviews. Molecular cell biology 3206 28974774
2008 AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell 3150 18439900
2007 AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proceedings of the National Academy of Sciences of the United States of America 2018 17609368
2009 AMPK in Health and Disease. Physiological reviews 1339 19584320
2016 Regulation and function of AMPK in physiology and diseases. Experimental & molecular medicine 897 27416781
2010 AMPK and SIRT1: a long-standing partnership? American journal of physiology. Endocrinology and metabolism 743 20103737
2017 AMPK signalling in health and disease. Current opinion in cell biology 641 28232179
2006 AMPK and cell proliferation--AMPK as a therapeutic target for atherosclerosis and cancer. The Journal of physiology 442 16613876
2008 SNF1/AMPK pathways in yeast. Frontiers in bioscience : a journal and virtual library 426 17981722
2014 AMPK at the nexus of energetics and aging. Cell metabolism 377 24726383
2005 AMPK, the metabolic syndrome and cancer. Trends in pharmacological sciences 364 15681023
2019 AMPK and Autophagy. Advances in experimental medicine and biology 361 31776981
2010 AMPK inhibition in health and disease. Critical reviews in biochemistry and molecular biology 326 20522000
2015 Degradation of AMPK by a cancer-specific ubiquitin ligase. Cell 308 25679763
2014 The AMP-activated protein kinase (AMPK) and cancer: many faces of a metabolic regulator. Cancer letters 283 24486219
2022 The AMPK pathway in fatty liver disease. Frontiers in physiology 274 36203933
2003 Roles of 5'-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. The Biochemical journal 269 12839490
2009 AMPK: Lessons from transgenic and knockout animals. Frontiers in bioscience (Landmark edition) 254 19273052
2018 Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. The Journal of biological chemistry 251 30232152
2019 Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer. Autophagy 246 31232177
2009 AMPK as a mediator of hormonal signalling. Journal of molecular endocrinology 242 19625456
2020 AMPK, Mitochondrial Function, and Cardiovascular Disease. International journal of molecular sciences 223 32679729
2013 AMPK: a contextual oncogene or tumor suppressor? Cancer research 213 23644529
2005 New roles for the LKB1-->AMPK pathway. Current opinion in cell biology 213 15780593
2021 Role of AMPK mediated pathways in autophagy and aging. Biochimie 202 34838647
2018 Structure and Physiological Regulation of AMPK. International journal of molecular sciences 194 30423971
2018 AMPK: Potential Therapeutic Target for Ischemic Stroke. Theranostics 192 30214637
2003 Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models. Biochemical Society transactions 186 12546688
2022 Emerging Role of cAMP/AMPK Signaling. Cells 183 35053423
2015 AMPK and autophagy in glucose/glycogen metabolism. Molecular aspects of medicine 179 26297963
2022 AMPK and the Adaptation to Exercise. Annual review of physiology 166 35143330
2019 Critical role of AMPK in redox regulation under glucose starvation. Redox biology 164 30853530
2006 Expanding role of AMPK in endocrinology. Trends in endocrinology and metabolism: TEM 164 16766204
2022 Role of AMPK in autophagy. Frontiers in physiology 163 36505072
2017 The lysosome: a crucial hub for AMPK and mTORC1 signalling. The Biochemical journal 157 28408430
2021 AMPK, metabolism, and vascular function. The FEBS journal 136 33825330
2012 AMPK at the crossroads of circadian clocks and metabolism. Molecular and cellular endocrinology 131 22750052
2014 ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAA/AMPK signaling in advanced atherosclerosis. Autophagy 122 25484082
2008 LKB1 and AMPK in cell polarity and division. Trends in cell biology 120 18314332
2017 AMPK orchestrates an elaborate cascade protecting tissue from fibrosis and aging. Ageing research reviews 112 28709692
2013 The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis. Biochemical Society transactions 105 23863160
2016 AMPK and Cancer. Experientia supplementum (2012) 104 27812982
2018 Hypothalamic AMPK and energy balance. European journal of clinical investigation 97 29999521
2010 AMPK and vasculoprotection. Pharmacology & therapeutics 96 21111758
2008 AMPK and transcriptional regulation. Frontiers in bioscience : a journal and virtual library 91 17981775
2024 ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis. Journal of translational medicine 90 38395901
2017 AMPK negatively regulates tensin-dependent integrin activity. The Journal of cell biology 89 28289092
2014 Is AMPK the savior of the failing heart? Trends in endocrinology and metabolism: TEM 81 25439672
2014 AMPK regulates histone H2B O-GlcNAcylation. Nucleic acids research 79 24692660
2023 AMPK and the Endocrine Control of Metabolism. Endocrine reviews 77 37115289
2018 Is TAK1 a Direct Upstream Kinase of AMPK? International journal of molecular sciences 75 30111748
2017 AMPK and cardiac remodelling. Science China. Life sciences 75 29170891
2016 PRKAA/AMPK restricts HBV replication through promotion of autophagic degradation. Autophagy 73 27305174
2022 AMPK: The key to ischemia-reperfusion injury. Journal of cellular physiology 71 36134582
2016 AMPK promotes osteogenesis and inhibits adipogenesis through AMPK-Gfi1-OPN axis. Cellular signalling 69 27283242
2012 LKB1 and AMPK: central regulators of lymphocyte metabolism and function. Immunological reviews 69 22889215
2010 Targeting AMPK for cardiac protection: opportunities and challenges. Journal of molecular and cellular cardiology 69 21147121
2022 The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK. Nature metabolism 68 36217034
2015 AMPK: a master energy regulator for gonadal function. Frontiers in neuroscience 67 26236179
2022 Circular CPM promotes chemoresistance of gastric cancer via activating PRKAA2-mediated autophagy. Clinical and translational medicine 66 35075806
2015 Induction of autophagy by valproic acid enhanced lymphoma cell chemosensitivity through HDAC-independent and IP3-mediated PRKAA activation. Autophagy 63 26735433
2012 Immunometabolism of AMPK in insulin resistance and atherosclerosis. Molecular and cellular endocrinology 63 22361321
2018 AMPK Function in Mammalian Spermatozoa. International journal of molecular sciences 62 30360525
2024 Lithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing. Nature 59 39695235
2013 Regulation of ion channels and transporters by AMP-activated kinase (AMPK). Channels (Austin, Tex.) 58 24366036
2018 AMPK: An Epigenetic Landscape Modulator. International journal of molecular sciences 57 30347687
2017 AMPK regulates immunometabolism in sepsis. Brain, behavior, and immunity 57 29109024
2021 Multifaceted Role of AMPK in Viral Infections. Cells 56 34066434
2017 EJE PRIZE 2017: Hypothalamic AMPK: a golden target against obesity? European journal of endocrinology 56 28232370
2020 Mechanism of Activation of AMPK by Cordycepin. Cell chemical biology 54 31991096
2018 Role of AMPK in atherosclerosis via autophagy regulation. Science China. Life sciences 54 29656339
2018 Reciprocal Regulation of AMPK/SNF1 and Protein Acetylation. International journal of molecular sciences 54 30366365
2010 The LKB1/AMPK polarity pathway. FEBS letters 54 21185289
2016 Hypothalamic AMPK as a Regulator of Energy Homeostasis. Neural plasticity 53 27547453
2020 Roles of AMP-Activated Protein Kinase (AMPK) in Mammalian Reproduction. Frontiers in cell and developmental biology 52 33330475
2015 AMPK activation can delay aging. Discoveries (Craiova, Romania) 52 32309575
2017 Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing. The Journal of biological chemistry 51 28615457
2020 AMPK: implications in osteoarthritis and therapeutic targets. American journal of translational research 48 33437352
2018 STIM2 interacts with AMPK and regulates calcium-induced AMPK activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 48 30335546
2016 AMPK in Neurodegenerative Diseases. Experientia supplementum (2012) 47 27812980
2016 Targeting AMPK for the Alleviation of Pathological Pain. Experientia supplementum (2012) 46 27812984
2009 Regulation of facilitative glucose transporters and AKT/MAPK/PRKAA signaling via estradiol and progesterone in the mouse uterine epithelium. Biology of reproduction 46 19208550
2024 AMPK: The energy sensor at the crossroads of aging and cancer. Seminars in cancer biology 45 39197808
2016 AMPK in Neurodegenerative Diseases: Implications and Therapeutic Perspectives. Current drug targets 45 26073858
2020 Energy stress inhibits ferroptosis via AMPK. Molecular & cellular oncology 44 32944623
2016 AMPK in Cardiovascular Diseases. Experientia supplementum (2012) 42 27812981
2024 Inhibition of PRKAA/AMPK (Ser485/491) phosphorylation by crizotinib induces cardiotoxicity via perturbing autophagosome-lysosome fusion. Autophagy 41 37733896
2018 AMPK in microvascular complications of diabetes and the beneficial effects of AMPK activators from plants. Phytomedicine : international journal of phytotherapy and phytopharmacology 41 30935723
2016 AMPK activates LXRα and ABCA1 expression in human macrophages. The international journal of biochemistry & cell biology 41 27343431
2024 Opposing roles for AMPK in regulating distinct mitophagy pathways. Molecular cell 39 39532100
2023 Neferine ameliorates nonalcoholic steatohepatitis through regulating AMPK pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 37 37031639
2017 Deletion of PRKAA triggers mitochondrial fission by inhibiting the autophagy-dependent degradation of DNM1L. Autophagy 37 28085543
2016 Structure and Regulation of AMPK. Experientia supplementum (2012) 36 27812974
2020 Genetic loss of AMPK-glycogen binding destabilises AMPK and disrupts metabolism. Molecular metabolism 35 32610071
2018 Natural activators of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and their pharmacological activities. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 35 30290216
2021 AMPK Localization: A Key to Differential Energy Regulation. International journal of molecular sciences 34 34681581
2018 AMP-Activated Protein (AMPK) in Pathophysiology of Pregnancy Complications. International journal of molecular sciences 34 30304773
2009 Cytokine Regulation of AMPK signalling. Frontiers in bioscience (Landmark edition) 34 19273172
2007 Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes. Molecular genetics and metabolism 34 17950019

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