Affinage

PRKAA1

5'-AMP-activated protein kinase catalytic subunit alpha-1 · UniProt Q13131

Round 2 corrected
Length
559 aa
Mass
64.0 kDa
Annotated
2026-04-28
69 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKAA1 encodes the catalytic α1 subunit of AMP-activated protein kinase (AMPK), a master energy sensor that coordinates cellular anabolism and catabolism in response to metabolic stress. Activated by phosphorylation at Thr-172 by LKB1 under energy stress or by CaMKKβ in response to Ca²⁺ signals (PMID:8910387, PMID:14985505, PMID:16054095), PRKAA1 directly phosphorylates substrates including ACC, TSC2, raptor, and ULK1 to inhibit mTORC1-driven growth, stimulate fatty acid oxidation, promote autophagy and mitophagy, and suppress ferroptosis (PMID:14651849, PMID:18439900, PMID:24988326, PMID:32029897). These activities underpin diverse physiological roles: PRKAA1-dependent mitophagy is essential for erythrocyte maturation and prevention of hemolytic anemia (PMID:24988326); endothelial PRKAA1 sustains protective glycolysis and vascular integrity against atherosclerosis (PMID:30405100); myeloid PRKAA1 modulates macrophage inflammatory polarization by suppressing NF-κB and promoting anti-inflammatory cytokine production (PMID:19050283, PMID:33511118); and muscle-specific PRKAA1 maintains lipid oxidative capacity and prevents intramyocellular lipid accumulation (PMID:29288408). Loss of PRKAA1 in erythroid progenitors causes hemolytic anemia with splenomegaly due to failed mitochondrial clearance, a phenotype rescued by rapamycin (PMID:24988326).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Identification of Thr-172 as the single essential activation-loop phosphorylation site on AMPK α resolved how upstream kinase input is transduced into catalytic activation and why AMP dependence requires prior phosphorylation.

    Evidence In vitro kinase assay with purified rat liver AMPK; phosphopeptide mapping and site-directed mutagenesis

    PMID:8910387

    Open questions at the time
    • Identity of the upstream kinase (AMPKK) was unknown
    • Structural basis of AMP-dependent allosteric activation unresolved
    • Relative contributions of α1 versus α2 isoforms not distinguished
  2. 2004 High

    Establishing LKB1 as the dominant upstream kinase for Thr-172 phosphorylation connected the tumor suppressor LKB1 to energy sensing and explained the near-complete loss of AMPK activity in LKB1-deficient cells.

    Evidence In vitro kinase assay; LKB1-knockout MEFs with WT vs kinase-dead LKB1 reintroduction; energy-stress apoptosis rescue

    PMID:14985505

    Open questions at the time
    • Whether alternative kinases can compensate in specific tissues remained unclear
    • The role of LKB1-associated regulatory subunits (STRAD, MO25) in directing specificity toward PRKAA1 vs PRKAA2 unresolved
  3. 2005 High

    Discovery of CaMKKβ as a Ca²⁺-dependent, AMP-independent upstream kinase for AMPK revealed a second activation axis, explaining how AMPK can be activated without energy deficit.

    Evidence CaMKK inhibitor STO-609; isoform-specific siRNA; Ca²⁺ ionophore stimulation in LKB1-null cells; cell-free kinase assays

    PMID:16054095

    Open questions at the time
    • Relative in vivo contribution of CaMKKβ vs LKB1 in different tissues not quantified
    • Other potential upstream kinases not excluded
  4. 2002 High

    Positioning PRKAA1 as a required mediator downstream of adiponectin and upstream of ACC phosphorylation and fatty acid oxidation established the first complete hormonal–AMPK–metabolic effector axis in muscle and liver.

    Evidence Dominant-negative AMPK epistasis; ACC phosphorylation; fatty acid oxidation and glucose uptake in myocytes

    PMID:12368907

    Open questions at the time
    • Whether PRKAA1 or PRKAA2 is the predominant isoform mediating adiponectin effects in vivo was not resolved
    • Receptor-to-AMPK signaling intermediates were unknown
  5. 2003 High

    Identification of TSC2 as a direct AMPK substrate linked energy sensing to growth control via mTOR, explaining how energy deprivation suppresses cell size and translation.

    Evidence In vitro AMPK kinase assay on TSC2; TSC2-null cell epistasis; cell size and apoptosis measurement

    PMID:14651849

    Open questions at the time
    • Whether AMPK phosphorylation of TSC2 is sufficient or requires cooperation with other TSC2 kinases
    • Direct in vivo relevance in tissue-specific contexts not shown
  6. 2005 High

    AMPK-dependent phosphorylation of p53 at Ser-15 connected the metabolic checkpoint to cell-cycle arrest, revealing that persistent AMPK activation can drive senescence rather than just survival.

    Evidence AICAR activation; p53-S15 phosphorylation; cell-cycle analysis; p53-null epistasis; glucose deprivation

    PMID:15866171

    Open questions at the time
    • Whether AMPK phosphorylates p53 directly or via intermediate kinases was not fully delineated
    • Threshold distinguishing protective arrest from senescence undefined
  7. 2008 High

    Identification of raptor as a direct AMPK substrate that recruits 14-3-3 upon phosphorylation provided a second, TSC2-independent mechanism for mTORC1 inhibition and clarified the multi-pronged nature of AMPK's control over growth.

    Evidence Proteomic substrate screen; in vitro kinase assay; 14-3-3 Co-IP; raptor phospho-mutant rescue; cell-cycle analysis

    PMID:18439900

    Open questions at the time
    • Relative quantitative contribution of raptor vs TSC2 phosphorylation to mTORC1 suppression unknown
    • Whether 14-3-3 binding is reversible and how it is terminated unclear
  8. 2008 High

    Demonstrating that PRKAA1 suppresses NF-κB-driven proinflammatory cytokines (TNF-α, IL-6) and promotes IL-10 in macrophages established a direct immune-regulatory role for the α1 isoform beyond metabolic regulation.

    Evidence Reciprocal gain/loss-of-function (dominant-negative and constitutively active AMPKα1) in macrophages; cytokine ELISA; IκB-α and Akt phosphorylation

    PMID:19050283

    Open questions at the time
    • Direct phosphorylation substrates mediating anti-inflammatory output not identified
    • In vivo relevance in infection or sterile inflammation not tested
  9. 2014 High

    Showing that PRKAA1 is essential for ULK1-Ser555 phosphorylation, BECN1 complex formation, and mitophagic clearance of mitochondria during erythropoiesis — with knockout mice developing hemolytic anemia — established a non-redundant physiological requirement for the α1 isoform in terminal differentiation.

    Evidence Prkaa1 knockout mice; bone marrow transplantation; ULK1-BECN1 Co-IP; mitochondrial content and ROS measurement; rapamycin rescue

    PMID:24988326

    Open questions at the time
    • Why PRKAA2 cannot compensate for PRKAA1 in erythroid cells is mechanistically unresolved
    • Precise signaling events linking PRKAA1 to ULK1-BECN1 assembly not fully mapped
  10. 2015 High

    Epistatic pathway dissection placed CaMKK2–PRKAA1–ULK1 as a required signaling axis for CSF1-induced autophagy during monocyte-to-macrophage differentiation, extending the mitophagy role to myeloid lineage commitment and identifying therapeutic restoration in CMML.

    Evidence Sequential siRNA knockdown of CAMKK2, PRKAA1, ULK1 in human monocytes; autophagy flux; differentiation markers; P2RY6 agonist rescue in CMML patient cells

    PMID:26029847

    Open questions at the time
    • Whether PRKAA1-dependent autophagy is required for all macrophage subtypes or only M-CSF-derived
    • Long-term efficacy of P2RY6 agonism in CMML patients unknown
  11. 2017 Medium

    Muscle-specific Prkaa1 deletion revealed that the α1 isoform maintains mitochondrial oxidative gene expression and prevents intramyocellular lipid accumulation, with mTOR hyperactivation as a contributing mechanism, extending PRKAA1's tissue-specific roles to skeletal muscle lipid homeostasis.

    Evidence Muscle-specific Prkaa1 knockout mice; HFD feeding; triglyceride and gene expression; mTOR pathway immunoblot

    PMID:29288408

    Open questions at the time
    • Relative contribution of PRKAA1 vs PRKAA2 in skeletal muscle lipid metabolism not clarified
    • Whether mTOR inhibition alone rescues the lipid phenotype not tested
    • Single-lab observation
  12. 2018 High

    Endothelial-specific Prkaa1 deletion showed that PRKAA1-driven glycolysis is required for endothelial proliferation and barrier integrity, and its loss accelerates atherosclerosis — a phenotype rescued by GLUT1 overexpression — establishing the α1 isoform as a vascular metabolic gatekeeper.

    Evidence EC-specific Prkaa1 KO mice; atherosclerosis quantification; GLUT1 rescue; ECAR measurement; barrier assays

    PMID:30405100

    Open questions at the time
    • Molecular targets through which PRKAA1 upregulates GLUT1 expression not identified
    • Interaction with endothelial PRKAA2 not addressed
  13. 2020 High

    Demonstrating that AMPK inhibits ferroptosis via ACC phosphorylation and consequent reduction of PUFA biosynthesis linked the classical AMPK-ACC axis to a novel cell death modality and provided in vivo validation in renal ischemia-reperfusion injury.

    Evidence Genetic AMPK inactivation; ferroptosis and lipidomic analysis; ACC phosphorylation; renal IRI model

    PMID:32029897

    Open questions at the time
    • Whether PRKAA1 or PRKAA2 is the dominant isoform in ferroptosis suppression not distinguished
    • Other AMPK substrates contributing to ferroptosis resistance not excluded
  14. 2021 High

    Dual context-dependent vascular roles emerged: endothelial PRKAA1 deficiency in HFD reduces acetyl-CoA and p300-mediated inflammatory transcription (improving metabolic syndrome), while myeloid PRKAA1 deficiency impairs macrophage metabolic fitness and tissue recruitment (reducing atherosclerosis), revealing opposing cell-type-specific outcomes.

    Evidence EC-specific and myeloid-specific Prkaa1 KO mice on HFD; acetyl-CoA and p300 activity; macrophage metabolomics; flow cytometry; atherosclerosis and metabolic phenotyping

    PMID:33511118 PMID:34796475

    Open questions at the time
    • How the same kinase produces pro- vs anti-inflammatory outcomes in different cell types is mechanistically incomplete
    • Interaction between endothelial and myeloid PRKAA1 in the same disease model not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include: the structural basis for α1 vs α2 isoform substrate specificity; how PRKAA1 integrates multiple upstream signals to produce context-dependent (protective vs pathological) outcomes in different tissues; and whether the tendon maintenance and neuronal memory functions represent conserved or tissue-specific AMPK signaling modules.
  • No crystal structure of full-length α1β1γ1 with physiological substrate bound
  • Isoform-specific interactomes not comprehensively mapped
  • Causal human genetic variants in PRKAA1 linked to Mendelian disease not yet reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 4
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-9612973 Autophagy 4 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ACACABECN1CAMKK2RPTORSTK11TP53TSC2ULK1
Complex memberships
AMPK (α1β1γ1 / α1β2γ1 heterotrimeric complex)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The upstream kinase (later identified as LKB1) phosphorylates the AMPK alpha subunit (PRKAA1) at a single major site, threonine 172, located in the activation segment between the DFG and APE motifs; this phosphorylation is absolutely required for AMP-dependent activation and is antagonized by high ATP concentrations. In vitro kinase assay with purified rat liver AMPK kinase cascade; site identification by phosphopeptide mapping and mutagenesis The Journal of biological chemistry High 8910387
2004 LKB1 serine/threonine kinase directly phosphorylates Thr-172 on the AMPK alpha subunit (PRKAA1) in vitro and in cells, serving as the dominant upstream activating kinase; LKB1-deficient cells show near-complete loss of Thr-172 phosphorylation and are hypersensitive to energy-stress-induced apoptosis. In vitro kinase assay; LKB1-knockout MEFs; reintroduction of WT vs kinase-dead LKB1; cell death assay under energy stress Proceedings of the National Academy of Sciences of the United States of America High 14985505
2005 CaMKKβ (calmodulin-dependent protein kinase kinase beta) is an alternative upstream kinase that phosphorylates and activates AMPK (PRKAA1) in a Ca2+-dependent, AMP-independent manner in LKB1-deficient cells; this represents a Ca2+-dependent neuroprotective pathway. CaMKK inhibitor STO-609; isoform-specific siRNA knockdown; Ca2+ ionophore stimulation in LKB1-null cells; cell-free kinase assays Cell metabolism High 16054095
2002 Adiponectin activates AMPK (including the alpha1/PRKAA1 subunit) in skeletal muscle and liver, stimulating phosphorylation of acetyl-CoA carboxylase, fatty-acid oxidation, and glucose uptake; dominant-negative AMPK blocks each of these effects, placing PRKAA1 downstream of adiponectin and upstream of ACC and fatty acid oxidation. Dominant-negative AMPK transfection; in vitro AMPK activity assay; ACC phosphorylation; fatty acid oxidation assay in myocytes; glucose uptake measurement Nature medicine High 12368907
2003 AMPK (PRKAA1) phosphorylates TSC2 under energy starvation, enhancing TSC2 activity to suppress mTOR-dependent translation and cell growth; TSC2 phosphorylation by AMPK is required for cell-size control and protection from energy-deprivation-induced apoptosis. In vitro AMPK kinase assay on TSC2; genetic epistasis with TSC2-null cells; cell size measurement; apoptosis assay under energy stress Cell High 14651849
2005 AMPK activation (involving PRKAA1) induces phosphorylation of p53 on serine 15, triggering a G1/S cell-cycle checkpoint in response to glucose deprivation; this AMPK-p53 axis promotes cellular survival during energy stress but drives senescence upon persistent activation. Pharmacological AMPK activation (AICAR); p53-S15 phosphorylation by immunoblot; cell-cycle analysis; p53-null cell epistasis; glucose deprivation survival assay Molecular cell High 15866171
2008 AMPK (PRKAA1) directly phosphorylates raptor on two conserved serine residues, inducing 14-3-3 binding to raptor; this phosphorylation is required for mTORC1 inhibition and cell-cycle arrest in response to energy stress, revealing raptor as a direct AMPK substrate mediating the metabolic checkpoint. Proteomic substrate screen; in vitro kinase assay with purified AMPK and raptor; 14-3-3 co-immunoprecipitation; raptor phospho-mutants; cell-cycle analysis in energy-stressed cells Molecular cell High 18439900
2008 AMPK alpha1 (PRKAA1) in macrophages suppresses LPS-induced proinflammatory cytokine production (TNF-α, IL-6) and promotes IL-10; dominant-negative AMPKα1 enhances inflammatory responses while constitutively active AMPKα1 reduces them; AMPK negatively regulates IκB-α degradation and positively regulates Akt/CREB signaling. siRNA knockdown; dominant-negative and constitutively active AMPKα1 transfection in macrophages; cytokine ELISA; IκB-α and Akt phosphorylation by immunoblot Journal of immunology High 19050283
2014 PRKAA1 is required for ULK1 phosphorylation at Ser555 and formation of ULK1-BECN1-PtdIns3K complexes necessary for autophagy-dependent mitochondrial clearance (mitophagy) during erythrocyte maturation; prkaa1−/− mice develop hemolytic anemia, splenomegaly, and shortened erythrocyte lifespan due to accumulation of damaged mitochondria and elevated ROS, all rescued by rapamycin or mitochondria-targeted antioxidant treatment. prkaa1 knockout mice; bone marrow transplantation; ULK1 Ser555 phosphorylation immunoblot; Co-IP of ULK1-BECN1 complex; autophagic flux assay; mitochondrial content and ROS measurement; hematologic parameters Autophagy High 24988326
2014 Autophagy is not required for exercise performance or PRKAA1 activation during physical activity, but autophagy (requiring PRKAA1-dependent signaling) is critical for mitochondrial quality control during damaging muscle contraction; this protective effect is gender-specific, primarily affecting females. Inducible muscle-specific Atg7 knockout mice; treadmill exercise testing; PRKAA1 activity assay; glucose homeostasis measurement; mitochondrial function assay Autophagy Medium 25483961
2015 The CAMKK2-PRKAA1-ULK1 signaling pathway is required for CSF1-induced autophagy and human monocyte-to-macrophage differentiation; PRKAA1 links P2RY6 receptor engagement to autophagy induction, and pharmacological P2RY6 agonists can restore autophagy and normal differentiation in CMML patient cells. siRNA knockdown of CAMKK2, PRKAA1, ULK1 in human monocytes; autophagy flux assay; differentiation markers; P2RY6 agonist treatment; primary CMML patient cells Autophagy High 26029847
2010 PRKAA1/2 mediates stress-induced proteasome-dependent loss of ID2 protein in trophoblast stem cells; at low stress levels, PRKAA1/2 mediates metabolic adaptation (ACC inactivation by phosphorylation) without ID2 loss, while higher stress drives irreversible TSC differentiation via ID2 loss. AMPK inhibitor compound C; PRKAA1/2 siRNA; proteasome inhibitor; ID2 immunoblot; ACC phosphorylation assay; cell accumulation assay in mouse TSCs Reproduction (Cambridge, England) Medium 20876741
2010 Benzo(a)pyrene (BaP) activates PRKAA1/2 and causes PRKAA1/2-dependent loss of ID2 protein in trophoblast stem cells in a dose-dependent manner; this occurs at BaP doses equivalent to approximately 2-3 pack/day smoking, suggesting a mechanism for implantation failure in smokers. AMPK activity assay; PRKAA1/2 siRNA in mouse TSCs; ID2 immunoblot; BaP dose-response; cell proliferation measurement Molecular reproduction and development Medium 20422711
2010 siRNA silencing of PRKAA1 (AMPKα1) in HEK293 cells increases susceptibility to methylmercury toxicity, while AICAR-mediated AMPK activation reduces toxicity, indicating that PRKAA1 phosphorylation/activation plays a protective role against methylmercury-induced cell death. siRNA knockdown of PRKAA1; AICAR pharmacological activation; cell viability assay after methylmercury treatment The Journal of toxicological sciences Low 20686348
2018 Selective endothelial deletion of Prkaa1 reduces glycolysis, compromises endothelial cell proliferation, and accelerates atherosclerotic lesion formation in hyperlipidemic mice; rescue of glycolysis via Slc2a1 (GLUT1) overexpression restores endothelial viability, barrier integrity, and reverses atherosclerosis susceptibility, placing PRKAA1-driven glycolysis upstream of endothelial protection. Endothelial-specific Prkaa1 knockout mice; atherosclerosis lesion quantification; Slc2a1 overexpression rescue; glycolysis measurement (ECAR); endothelial barrier assay; human EC siRNA knockdown Nature communications High 30405100
2019 PRKAA1 promotes gastric cancer cell proliferation and inhibits apoptosis through activation of JNK1 and Akt signaling pathways; pharmacological inhibition (compound C) or shRNA knockdown of PRKAA1 reduces PCNA and Bcl-2 expression and blocks JNK1/Akt activity; inactivation of JNK1 or Akt reverses PRKAA1 overexpression-induced proliferation. shRNA knockdown; AMPK inhibitor compound C; JNK1/Akt inhibitors; PCNA/Bcl-2 immunoblot; xenograft tumor growth assay in nude mice Oncology research Medium 31558185
2019 NF-κBp50 transcriptionally regulates PRKAA1 expression in response to H. pylori infection; PRKAA1 in turn activates NF-κB signaling and promotes MMP-2 expression, gastric cancer cell invasion and migration; knockdown of PRKAA1 reduces metastasis in nude mice. NF-κBp50 siRNA; PRKAA1 stable shRNA knockdown; MMP-2 immunoblot; invasion/migration assay; lung metastasis xenograft model Artificial cells, nanomedicine, and biotechnology Medium 31841039
2020 Energy stress activates AMPK (PRKAA1), which inhibits ferroptosis partly through AMPK-mediated phosphorylation of acetyl-CoA carboxylase (ACC) and consequent reduction of polyunsaturated fatty acid biosynthesis; AMPK inactivation abolishes the protective effects of energy stress on ferroptosis in vitro and in renal ischemia-reperfusion injury in vivo. AMPK genetic inactivation; energy-stress treatments; ferroptosis assay; lipidomic analysis; ACC phosphorylation; renal IRI mouse model Nature cell biology High 32029897
2021 Endothelial PRKAA1 deficiency in HFD-fed mice unexpectedly alleviates metabolic syndrome; mechanistically, PRKAA1 knockdown in ECs reduces glycolysis and fatty acid oxidation, decreases acetyl-CoA levels, and suppresses inflammatory gene transcription mediated by ATP citrate lyase and histone acetyltransferase p300. EC-specific Prkaa1 knockout mice on HFD; metabolic phenotyping; EC glycolysis/FAO measurement; acetyl-CoA quantification; p300 histone acetyltransferase activity; inflammatory gene expression British journal of pharmacology High 34796475
2021 Myeloid-specific Prkaa1 deficiency downregulates glucose and lipid metabolism genes in macrophages, impairs their metabolic fitness, and suppresses monocyte/macrophage recruitment to adipose tissue, liver, and arterial walls, reducing atherosclerosis, adipose inflammation, and HFD-induced metabolic disorders. Myeloid-specific Prkaa1 knockout mice; metabolic gene expression; macrophage glucose/lipid metabolism assays; flow cytometry of tissue macrophages; atherosclerosis lesion quantification Frontiers in cell and developmental biology Medium 33511118
2022 FTO demethylase stabilizes PRKAA1 mRNA by reducing m6A modification at the 3'-UTR, preventing YTHDF2-mediated degradation; increased PRKAA1 protein promotes gastric cancer cell growth and glycolysis while suppressing apoptosis by regulating the redox balance (GSH, NADPH levels). RNA immunoprecipitation (m6A-RIP); YTHDF2 interaction assay with PRKAA1 3'-UTR; FTO siRNA/overexpression; PRKAA1 silencing/overexpression; lactic acid, GSH, NADP+/NADPH measurement; ECAR analysis Neoplasma Medium 36305690
2023 PRKAA1 activation induces aberrant PINK1/Parkin-dependent mitophagy in fluoride-exposed neurons; sodium fluoride increases PRKAA1 phosphorylation and upregulates PINK1, Parkin, TOMM20, and Cyt C; both AMPK inhibitor (dorsomorphin) and autophagy inhibitor (3-MA) rescue NaF-induced neuronal apoptosis by restoring normal mitophagic flux. NaF-treated SH-SY5Y cells and rat model; phosphoproteomics; PINK1/Parkin/TOMM20 immunoblot; autophagic flux assay; dorsomorphin and 3-MA pharmacological rescue; apoptosis assay Ecotoxicology and environmental safety Medium 36924562
2017 Muscle-specific deletion of Prkaa1 delays skeletal muscle development and, under high-fat diet, leads to enhanced intramyocellular lipid accumulation with upregulation of adipogenic genes and downregulation of mitochondrial oxidation genes; Prkaa1 deletion also activates skeletal muscle mTOR signaling, which contributes to impaired lipid metabolism. Muscle-specific Prkaa1 knockout mice; HFD feeding; intramyocellular triglyceride quantification; adipogenic and mitochondrial gene expression; mTOR pathway immunoblot; glucose tolerance and insulin sensitivity tests Journal of physiology and biochemistry Medium 29288408
2024 GENT (gentiacaulein) inhibits glucose transport, raising the AMP:ATP ratio and activating PRKAA1-mediated autophagy in astrocytes; increased PRKAA1-dependent autophagy enhances clearance of amyloid-β; PRKAA1 knockdown reverses GENT-induced autophagy and anti-inflammatory effects, confirming PRKAA1 as the mechanistic link between energy sensing and Aβ clearance. Pharmacological glucose transport inhibition; AMP:ATP ratio measurement; PRKAA1 siRNA knockdown; autophagy flux assay; Aβ clearance quantification; NF-κB nuclear translocation assay; cytokine measurement Autophagy reports Medium 40395536
2025 Selective deletion of Prkaa1 in tendon progenitors causes normal postnatal development but progressive tendon pathology: by one month, widespread transcriptional changes in cell cycle regulation and ECM organization appear; by three months, AMPKα1-deficient tendons show reduced mechanical strength, elevated senescence markers (p21, p16), and eventual ectopic calcification; in vitro, tendon fibroblasts lacking AMPKα1 have altered ECM substrate adhesion; voluntary exercise partially rescues these deficits by improving ECM organization and reducing senescence. Conditional Prkaa1 knockout in tendon progenitors; RNA sequencing; mechanical tensile testing; senescence marker immunostaining; ectopic calcification histology; ECM adhesion assay; voluntary exercise intervention bioRxivpreprint Medium bio_10.1101_2025.01.31.635920
2017 miR-181a targets PRKAA1 in hippocampal neurons (validated by luciferase reporter assay); CFC/OLT training transiently increases miR-181a and decreases PRKAA1 expression/activity; microinjection of PRKAA1 agonist AICAR or inhibitor compound C in the dorsal hippocampus reverses the effects of miR-181a manipulation on memory formation, placing PRKAA1 downstream of miR-181a in hippocampus-dependent memory consolidation. Luciferase reporter assay; miR-181a agomir/antagomir injection; PRKAA1 activity measurement; AICAR/compound C hippocampal microinjection; fear conditioning and object location behavioral tests Scientific reports Medium 28814760

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nature medicine 3297 12368907
2003 TSC2 mediates cellular energy response to control cell growth and survival. Cell 3187 14651849
2008 AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell 3139 18439900
2011 The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nature cell biology 2435 21892142
2005 AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell metabolism 2232 16054041
2004 The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proceedings of the National Academy of Sciences of the United States of America 1500 14985505
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2005 AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Molecular cell 1363 15866171
2005 Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell metabolism 1350 16054095
2010 Network organization of the human autophagy system. Nature 1286 20562859
2004 LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. The EMBO journal 1153 14976552
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1996 Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. The Journal of biological chemistry 1041 8910387
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Current biology : CB 983 12906785
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2008 AMPK and PPARdelta agonists are exercise mimetics. Cell 977 18674809
2020 Energy-stress-mediated AMPK activation inhibits ferroptosis. Nature cell biology 928 32029897
2016 Regulation and function of AMPK in physiology and diseases. Experimental & molecular medicine 888 27416781
2004 The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer cell 883 15261145
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2017 Roles of tau protein in health and disease. Acta neuropathologica 716 28386764
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2002 AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. The Journal of biological chemistry 687 11997383
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2014 Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell 645 24529379
2008 Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. Journal of immunology (Baltimore, Md. : 1950) 645 19050283
2014 Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity. Autophagy 122 25483961
2018 PRKAA1/AMPKα1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis. Nature communications 117 30405100
2014 Maternal PRKAA1 and EDNRA genotypes are associated with birth weight, and PRKAA1 with uterine artery diameter and metabolic homeostasis at high altitude. Physiological genomics 94 25225183
2015 The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML. Autophagy 88 26029847
2014 Gene of the month. AMP kinase (PRKAA1). Journal of clinical pathology 49 24895169
2017 LINC00152/miR-139-5p regulates gastric cancer cell aerobic glycolysis by targeting PRKAA1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 45 29156518
2010 Cellular stress causes reversible, PRKAA1/2-, and proteasome-dependent ID2 protein loss in trophoblast stem cells. Reproduction (Cambridge, England) 39 20876741
2006 Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer. Gynecologic oncology 38 16595147
2018 High glucose suppresses the viability and proliferation of HTR‑8/SVneo cells through regulation of the miR‑137/PRKAA1/IL‑6 axis. International journal of molecular medicine 37 29786111
2014 PRKAA1/AMPKα1 is required for autophagy-dependent mitochondrial clearance during erythrocyte maturation. Autophagy 34 24988326
2013 Genetic variations in the PRKAA1 and ZBTB20 genes and gastric cancer susceptibility in a Korean population. Molecular carcinogenesis 31 23861218
2010 Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells. Molecular reproduction and development 31 20422711
2017 miR-181a involves in the hippocampus-dependent memory formation via targeting PRKAA1. Scientific reports 29 28814760
2019 LINC00473/miR-497-5p Regulates Esophageal Squamous Cell Carcinoma Progression Through Targeting PRKAA1. Cancer biotherapy & radiopharmaceuticals 28 31584290
2018 TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer. Journal of gastrointestinal and liver diseases : JGLD 24 30574617
2022 Inhibition of miR-130b-3p restores autophagy and attenuates intervertebral disc degeneration through mediating ATG14 and PRKAA1. Apoptosis : an international journal on programmed cell death 23 35435532
2019 PRKAA1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells Through Activating JNK1 and Akt Pathways. Oncology research 23 31558185
2023 Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 36906969
2022 PRKAA1, stabilized by FTO in an m6A-YTHDF2-dependent manner, promotes cell proliferation and glycolysis of gastric cancer by regulating the redox balance. Neoplasma 21 36305690
2023 PRKAA1 induces aberrant mitophagy in a PINK1/Parkin-dependent manner, contributing to fluoride-induced developmental neurotoxicity. Ecotoxicology and environmental safety 16 36924562
2014 Risk of gastric cancer is associated with PRKAA1 gene polymorphisms in Koreans. World journal of gastroenterology 16 25024613
2021 CircC6orf132 Facilitates Proliferation, Migration, Invasion, and Glycolysis of Gastric Cancer Cells Under Hypoxia by Acting on the miR-873-5p/PRKAA1 Axis. Frontiers in genetics 14 34659329
2020 Expression and Impact of Vaspin on In Vitro Oocyte Maturation through MAP3/1 and PRKAA1 Signalling Pathways. International journal of molecular sciences 14 33302416
2017 Muscle-specific deletion of Prkaa1 enhances skeletal muscle lipid accumulation in mice fed a high-fat diet. Journal of physiology and biochemistry 14 29288408
2019 Involvement of NF-κB signaling pathway in the regulation of PRKAA1-mediated tumorigenesis in gastric cancer. Artificial cells, nanomedicine, and biotechnology 13 31841039
2021 Endothelial AMPKα1/PRKAA1 exacerbates inflammation in HFD-fed mice. British journal of pharmacology 12 34796475
2010 siRNA-mediated AMPKalpha1 subunit gene PRKAA1 silencing enhances methylmercury toxicity in HEK293 cells. The Journal of toxicological sciences 12 20686348
2016 Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans. Cancer medicine 11 27726301
2021 Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders. Frontiers in cell and developmental biology 10 33511118
2018 Association between PRKAA1 rs13361707 T>C polymorphism and gastric cancer risk: Evidence based on a meta-analysis. Medicine 7 29620653
2023 Association of PTGER4 and PRKAA1 genetic polymorphisms with gastric cancer. BMC medical genomics 6 37670284
2022 Circ_0003340 downregulation mitigates esophageal squamous cell carcinoma progression by targeting miR-940/PRKAA1 axis. Thoracic cancer 6 35297212
2018 Genetic variations in PRKAA1 predict the risk and progression of gastric Cancer. BMC cancer 6 30253744
2024 Gentiacaulein inhibits glucose transport to induce PRKAA1-mediated autophagy to clear amyloid beta and associated inflammation in primary astrocytes. Autophagy reports 4 40395536
2023 Genetic polymorphisms of PRKAA1 (AMPKα1) and postherpetic pain susceptibility: Multicenter, randomized control, and haplotype analysis study. Frontiers in molecular neuroscience 3 36818655
2020 PRKAA1 rs13361707 C/T polymorphism confers decreased susceptibility to esophageal cancer: A case-control study. Journal of clinical laboratory analysis 3 32488984
2016 Association of PRKAA1 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 3 27612659
2025 Adaptive PRKAA1 variant in Andeans is associated with improved ventilation and sleep phenotypes. iScience 2 40703441
2024 miR-181a expressed in the dorsal hippocampus regulates the reinstatement of cocaine CPP by targeting PRKAA1. Behavioural brain research 0 38878971