Affinage

PRKG1

cGMP-dependent protein kinase 1 · UniProt Q13976

Length
671 aa
Mass
76.4 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKG1 encodes cGMP-dependent protein kinase type I (PKG-1), a serine/threonine kinase that transduces nitric oxide/cGMP signaling into control of vascular smooth-muscle tone, cardiac remodeling, and cell survival (PMID:23910461, PMID:30700906, PMID:22270721). The single-copy gene generates Iα and Iβ isoforms through alternative first exons that differ only in their N-terminal regions (PMID:9192852). Activation is governed by cyclic nucleotide binding to the regulatory domain: crystallography and SAXS show two regulatory domains forming a symmetric dimer in which cGMP bound at the high-affinity B pockets provides critical inter-subunit contacts to drive an active conformation structurally distinct from PKA (PMID:27066748), while NMR analysis establishes that cGMP acts through two-state conformational selection and cAMP is only a partial agonist that samples a third, partially autoinhibited state (PMID:26370085). The N-terminal leucine zipper additionally carries C42, which forms an interchain disulfide upon oxidation that stabilizes the dimer (PMID:26132214) and, in stressed cardiomyocytes, drives PDE5 activation and PKG1α–PDE5 colocalization that underlies the antihypertrophic benefit of PDE5 inhibition (PMID:29545395). Once active, PKG-1 phosphorylates a broad substrate network: it phosphorylates TSC2 (S1364/S1365) to activate its RHEB-GAP function, suppressing stress-stimulated mTORC1 and thereby limiting cardiac hypertrophy and promoting autophagy (PMID:30700906); PKG1β forms a trimeric complex with IRAG and IP3 receptor type I at the ER, where phosphorylation of IRAG reduces IP3-mediated Ca2+ release to mediate smooth-muscle relaxation and platelet inhibition (PMID:21666108); it phosphorylates VASP at Ser239 to drive a phosphorylation-dependent VASP–TRPC4 interaction that inhibits store-operated cation entry (PMID:17913834); and it phosphorylates ENSA (S109) and ARPP19 (S104) at sites distinct from the MASTL-targeted residues in human platelets. A gain-of-function mutation, p.Arg177Gln, disrupts cGMP binding and renders PKG-1 constitutively active, causing familial thoracic aortic aneurysms and acute aortic dissections (PMID:23910461).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 Medium

    Defining the gene architecture established that a single PRKG1 locus produces the two type I PKG isoforms, explaining how isoform-specific N-terminal functions arise from one gene.

    Evidence Gene cloning, 5'-RACE, Northern blot, and exon mapping

    PMID:9192852

    Open questions at the time
    • Does not assign distinct functions or tissue distributions to Iα versus Iβ
    • Regulatory elements driving the alternative first exons not characterized
  2. 2007 Medium

    Identification of VASP-Ser239 phosphorylation and a phospho-dependent VASP–TRPC4 association revealed a molecular mechanism by which PKG-1α inhibits store-operated calcium entry.

    Evidence Ca2+ imaging, co-IP, immunocytochemistry, and PKG-1α inhibitor (DT-3) in glomerular mesangial cells

    PMID:17913834

    Open questions at the time
    • Direct phosphorylation by PKG-1α not reconstituted in vitro
    • How pVASP physically inhibits TRPC4 gating unresolved
  3. 2007 Medium

    Linking the cGMP/PKG pathway to mitochondrial KATP channel opening and Zn2+/ERK signaling connected PKG activity to cardioprotection against oxidative stress.

    Evidence Fluorescence imaging of Zn2+ and mitochondrial membrane potential with pharmacological probes in adult rat cardiomyocytes

    PMID:17570352

    Open questions at the time
    • Direct PKG substrate mediating Zn2+ release not identified
    • Relies on pharmacological inhibitors rather than genetic loss-of-function
  4. 2010 Medium

    Demonstrating that PKG inhibits TCF/β-catenin transcription via CTNNB1 repression and FOXO4-dependent sequestration extended PKG signaling into tumor-relevant transcriptional control.

    Evidence Luciferase reporters, co-IP, FOXO4 siRNA, and nuclear fractionation in colon cancer cells

    PMID:20348951

    Open questions at the time
    • Direct PKG substrate in the JNK/FOXO4 axis not defined
    • Single cell-type context
  5. 2011 Medium

    Isoform-specific assembly of a PKG1β–IRAG–IP3R-I complex explained how cGMP suppresses ER calcium release for smooth-muscle relaxation and platelet inhibition.

    Evidence Co-IP, isoform-specific interaction mapping, and phosphorylation/functional assays in smooth muscle and platelets

    PMID:21666108

    Open questions at the time
    • Summarized from prior reports rather than a single primary dataset
    • Structural basis of the trimeric complex unknown
  6. 2012 High

    Prkg1 knockout established an endogenous cGMP-PKG protective pathway in cochlear hair cells and neurons, broadening PKG function beyond the vasculature.

    Evidence Prkg1 knockout mice, auditory brainstem responses, PDE5-inhibitor rescue, and PAR immunostaining

    PMID:22270721

    Open questions at the time
    • Direct PKG substrates mediating hair-cell survival not identified
    • Mechanistic link between PKG and PAR upregulation unresolved
  7. 2013 High

    A constitutively activating p.Arg177Gln mutation directly linked PRKG1 to a Mendelian aortic disease, showing that unregulated kinase activity disrupts smooth-muscle contraction.

    Evidence Exome/Sanger sequencing, kinase and myosin light-chain phosphorylation assays in patient fibroblasts, LOD analysis across families

    PMID:23910461

    Open questions at the time
    • Full substrate consequences of constitutive activity in vascular cells not mapped
    • Tissue-specificity of the aortic phenotype not mechanistically explained
  8. 2014 Medium

    Multiple studies placed PKG within distinct upstream and downstream signaling contexts—heparin antiproliferative signaling, hypoxic miR-20a repression, and PVAT anticontractile function—defining its position in vascular regulation.

    Evidence PKG siRNA/inhibitors with ERK-Elk-1-MKP-1 readouts; miR-20a coding-region target mapping; PKG−/− mouse myography (years 2014, 2019)

    PMID:24095868 PMID:24911927 PMID:25447536

    Open questions at the time
    • Direct PKG substrates in each context largely undefined
    • Cross-talk among these vascular roles not integrated
  9. 2015 High

    Biophysical and structural work resolved the activation mechanism: cGMP-driven two-state selection versus cAMP partial agonism, leucine-zipper C42 disulfide dimer stabilization, and a downstream CSE/H2S cardioprotective output.

    Evidence NMR of CNB-B; crystal structures of WT and C42L leucine zipper; adenoviral PKGIα/K390A with CSE inhibition in I/R models

    PMID:26036467 PMID:26132214 PMID:26370085

    Open questions at the time
    • How CNB-B conformational states couple to full-length kinase activation in vivo not shown
    • Direct PKG substrate inducing CSE not identified
  10. 2016 High

    The cGMP-bound regulatory-domain crystal structure defined the active dimer interface and showed PKG's active conformation is distinct from PKA, providing a structural framework for cyclic-nucleotide selectivity.

    Evidence X-ray crystallography at 2.5 Å, SAXS, and site-directed mutagenesis

    PMID:27066748

    Open questions at the time
    • Full-length holoenzyme structure not solved
    • Conformational transition to the catalytic domain not visualized
  11. 2018 High

    Redox-dead C42S knock-in mice demonstrated that C42 oxidation governs PKG1α-PDE5 colocalization and the therapeutic response to PDE5 inhibition, tying the structural disulfide to a subcellular signaling microdomain.

    Evidence PKG1αC42S knock-in mice, transaortic constriction, activity assays, immunofluorescence colocalization, pharmacological dissection

    PMID:29545395

    Open questions at the time
    • Mechanism by which oxidized PKG1α activates PDE5 not defined
    • Generality beyond cardiac stress unknown
  12. 2019 High

    Identification of TSC2-S1364/S1365 as a direct PKG substrate, validated by phospho-mutant knock-in mice, established PKG's antihypertrophic and pro-autophagic action through mTORC1 suppression.

    Evidence In vitro kinase assay, phospho-specific antibodies, TSC2-S1365A/S1365E knock-in mice, transaortic constriction, echocardiography

    PMID:30700906

    Open questions at the time
    • Stress-specific selectivity over basal mTORC1 not fully explained
    • Whether the same axis operates in non-cardiac tissues not established here
  13. 2019 Medium

    An sGC→cGMP→PKG→p38→PGC-1α epistasis defined a PKG-driven mitochondrial biogenesis program in renal proximal tubule cells.

    Evidence Pharmacological PKG and p38 inhibitors in vitro and in vivo, nuclear phospho-PGC-1α fractionation, biogenesis markers

    PMID:31841384

    Open questions at the time
    • Direct PKG substrate upstream of p38 not identified
    • Reliance on pharmacological epistasis without genetic PKG deletion
  14. 2020 Medium

    Reconstitution showing PKG phosphorylates ENSA-S109 and ARPP19-S104 at sites distinct from MASTL targets revealed PKG input into the PP2A-regulatory module in anucleate platelets.

    Evidence Platelet proteomics, recombinant PKG kinase assays with ENSA/ARPP19 phospho-mutants, cGMP-elevating agents

    PMID:32085646

    Open questions at the time
    • Functional consequence of these phosphorylations for PP2A activity in platelets not resolved
    • Single-lab finding
  15. 2024 Medium

    Placing PRKG1 upstream of PINK1 and the STING/IRF3 axis connected PKG to mitochondrial quality control and inflammatory suppression in cardiotoxicity.

    Evidence AAV-mediated cardiac PRKG1 overexpression/silencing, RNA-seq, PINK1/STING/IRF3 Western blots, mitochondrial assays in mouse models

    PMID:39059761

    Open questions at the time
    • Direct PKG substrate activating PINK1 not identified
    • Whether the effect is kinase-dependent not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How isoform-specific targeting, redox state, and the diverse substrate set are integrated into tissue-specific PKG outputs remains unresolved.
  • No full-length holoenzyme structure capturing activation
  • Unified substrate-selectivity logic across cardiac, vascular, renal, and platelet contexts not established
  • Mechanism coupling C42 oxidation to specific substrate phosphorylation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0060089 molecular transducer activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-397014 Muscle contraction 3 R-HSA-109582 Hemostasis 1 R-HSA-9612973 Autophagy 1
Partners
ARPP19ENSAIRAG1ITPR1PDE5ATRPC4TSC2VASP
Complex memberships
PKG1β–IRAG–IP3R-I ER complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 A gain-of-function missense mutation in PRKG1 (p.Arg177Gln) disrupts binding to the high-affinity cGMP binding site within the regulatory domain, rendering PKG-1 constitutively active even in the absence of cGMP. This constitutive activity leads to decreased phosphorylation of the myosin regulatory light chain in fibroblasts, predicted to cause decreased contraction of vascular smooth-muscle cells, and causes familial thoracic aortic aneurysms and acute aortic dissections. Exome sequencing, Sanger sequencing, functional assay of PKG-1 activity and myosin light chain phosphorylation in patient fibroblasts, LOD score analysis American Journal of Human Genetics High 23910461
2019 PKG1 (PRKG1) phosphorylates TSC2 at S1365 (mouse) / S1364-S1365 (human) in cardiomyocytes and fibroblasts. This phosphorylation activates TSC2's GTPase-activating function toward RHEB, thereby inhibiting stress-stimulated mTORC1 activity without altering basal mTORC1. PKG1-mediated TSC2 phosphorylation is required for PKG1's suppression of hypertrophy and stimulation of autophagy in cardiomyocytes under pressure overload. In vitro kinase assay, phospho-specific antibodies, homozygous knock-in mice (TSC2-S1365A phosphosilencing and S1365E phosphomimicking), transaortic constriction model, echocardiography, cell culture gain/loss-of-function Nature High 30700906
1997 PRKG1 is a single-copy gene with 19 exons spanning at least 220 kb that encodes both the type Iα and type Iβ isoforms of cGMP-dependent protein kinase via alternative first exons. The two isoforms differ only in their N-terminal regions, each driven by distinct transcription initiation sites. Several splice sites are conserved with the Drosophila DG2 gene and correlate with boundaries between functional domains of type I cGK. Gene cloning, 5′-RACE, Northern blot analysis, exon mapping Genomics Medium 9192852
2016 Crystal structure of the PKG Iα regulatory domain bound to cGMP at 2.5 Å reveals that two regulatory domains form a symmetric dimer in which cGMP molecules bound at the high-affinity (B) pockets provide critical inter-subunit contacts. Small-angle X-ray scattering and mutagenesis support the dimer model and indicate the dimer interface modulates kinase activation. The active conformation of PKG is structurally distinct from that of protein kinase A. X-ray crystallography (2.5 Å), small-angle X-ray scattering (SAXS), site-directed mutagenesis Structure High 27066748
2015 cAMP is a partial agonist for PKG Iα. NMR analysis of the cyclic nucleotide-binding domain B shows that cGMP activation follows a two-state conformational selection model, whereas cAMP partial agonism arises from sampling of a third, partially autoinhibited conformational state not accessed by cGMP. NMR spectroscopy of apo, cGMP-bound, and cAMP-bound forms of PKG cyclic nucleotide-binding domain B; comparative conformational analysis Journal of Biological Chemistry High 26370085
2015 The N-terminal leucine zipper (LZ) domain of PKG Iα contains C42, which forms an interchain disulfide bond upon oxidation. Crystal structures of wild-type and C42L mutant LZ domains show that the C42–C42′ disulfide bond dramatically stabilizes the PKG Iα dimer, and the C42L mutant mimics the structural conformation of the oxidized wild-type LZ. X-ray crystallography of wild-type and C42L leucine zipper domains, structural comparison Biochemistry High 26132214
2018 PKG1α oxidation at C42 (forming a homodimer disulfide) contributes to PDE5 activation and co-localization of PDE5 with PKG1α in stressed cardiomyocytes. Knock-in mice expressing redox-dead PKG1α (C42S) show minimal PDE5 activation after pressure overload and little colocalization of PDE5 with PKG1αC42S, resulting in loss of the antihypertrophic/antifibrotic benefit of PDE5 inhibition (sildenafil) but not sGC stimulation (BAY602770). Knock-in mouse model (PKG1αC42S), transaortic constriction, PKG activity assay, immunofluorescence co-localization, cardiac phenotyping Circulation: Heart Failure High 29545395
2011 PKG1β (but not PKG1α) forms a trimeric complex with IRAG (inositol trisphosphate receptor-associated cGMP-kinase substrate) and IP3 receptor type I at the endoplasmic reticulum. Phosphorylation of IRAG by PKG1β upon cGMP stimulation reduces IP3-mediated intracellular calcium release, thereby mediating smooth muscle relaxation and inhibition of platelet activation. Co-immunoprecipitation, isoform-specific interaction mapping, phosphorylation assays, functional studies in smooth muscle and platelets American Journal of Physiology: Heart and Circulatory Physiology Medium 21666108
2007 PKG-1α mediates inhibition of the store-operated cation channel (SOC/TRPC4) in human glomerular mesangial cells via phosphorylation of VASP at Ser239. PKG-1α-phosphorylated VASP (pSer239-VASP) associates with TRPC4 by co-immunoprecipitation and co-immunostaining, while unphosphorylated VASP does not, demonstrating a phosphorylation-dependent interaction that underlies SOC inhibition. Fura-2 Ca2+ imaging, RT-PCR, Western blotting, immunocytochemistry, co-immunoprecipitation, specific PKG-1α inhibitor (DT-3), 8-Br-cGMP American Journal of Physiology: Renal Physiology Medium 17913834
2012 Genetic deletion of Prkg1 in mice leads to greater vulnerability to and reduced recovery from noise-induced hearing loss (NIHL). Prkg1 is expressed in cochlear hair cells and neurons and partially overlaps with PDE5 expression. Pharmacological elevation of cGMP by vardenafil (PDE5 inhibitor) almost completely prevented NIHL in a Prkg1-dependent manner, and induced poly(ADP-ribose) (PAR) upregulation in hair cells and spiral ganglion via Prkg1, indicating an endogenous cGMP-Prkg1 protective signaling pathway in the inner ear. Prkg1 knockout mice, auditory brainstem response measurements, immunohistochemistry for Prkg1 and Pde5, vardenafil treatment, PAR immunostaining Nature Medicine High 22270721
2010 PKG activation in colon cancer cells inhibits TCF-dependent transcription through two mechanisms: (1) transcriptional repression of the CTNNB1 (β-catenin) gene, reducing β-catenin mRNA and protein; and (2) JNK-dependent sequestration of β-catenin by FOXO4, which requires nuclear translocation of FOXO4. FOXO4-specific siRNA completely blocked PKG's inhibitory effect on TCF activity. Luciferase reporter assays (CTNNB1 and TCF promoters), Western blotting, co-immunoprecipitation (β-catenin/FOXO4), siRNA knockdown, nuclear fractionation Oncogene Medium 20348951
2007 In isolated adult rat cardiomyocytes, NO mobilizes intracellular free Zn2+ via the cGMP/PKG pathway through opening of mitochondrial K(ATP) channels. PKG inhibitor KT5823 blocked Zn2+ release by SNAP, while the PKG activator 8-Br-cGMP mimicked NO action. The released Zn2+ activates ERK, which mediates protection against H2O2-induced loss of mitochondrial membrane potential. Fluorescence imaging (Newport Green DCF for Zn2+, TMRE for mitochondrial membrane potential), pharmacological inhibitors/activators (KT5823, 8-Br-cGMP, ODQ, NS2028, 5-HD, diazoxide, PD98059), Western blot for ERK phosphorylation Cardiovascular Research Medium 17570352
2015 PKG-Iα overexpression in cardiomyocytes and mice induces expression of the H2S-producing enzyme cystathionine-γ-lyase (CSE), increasing H2S levels, without affecting CBS or MPST. Inhibition of CSE by PAG abolishes the cardioprotective effect of PKG-Iα against ischemia/reperfusion injury in vitro and in vivo, indicating H2S is a downstream mediator of PKG-Iα cardioprotection. An inactive kinase-dead mutant (K390A) does not induce CSE, confirming kinase-dependent mechanism. Adenoviral overexpression of PKGIα and inactive K390A mutant, in vitro ischemia/reperfusion (necrosis/apoptosis assays), in vivo mouse I/R (infarct size, echocardiography), Western blotting for CSE/CBS/MPST, H2S measurement, CSE inhibitor (PAG) Basic Research in Cardiology Medium 26036467
2019 PKG (PRKG1) is required for the anticontractile function of perivascular adipose tissue (PVAT) in mouse resistance arteries. PKG−/− arteries lack PVAT anticontractile function, and DT-2/ODQ inhibition of PKG in PKG+/+ arteries recapitulates this loss. PKG activation by ANP rescues hypoxia-induced loss of PVAT function only in PKG+/+ mice. PKG is also necessary for normal paracrine signaling from adipocytes to smooth muscle and endothelium, and its absence reduces adipocyte adiponectin expression. Wire myography, PKG−/− mice, adiponectin−/− mice, pharmacological inhibitors (DT-2, ODQ), ANP stimulation, solution transfer experiments Cardiovascular Research Medium 24095868
2014 miR-20a, upregulated by hypoxia in pulmonary artery smooth muscle cells, directly represses PRKG1 expression by targeting two binding sites within the coding region (not the 3′ UTR) of PRKG1 mRNA. Functional studies showed miR-20a promotes PASMC proliferation and migration while inhibiting differentiation, phenocopying loss of PRKG1. miRNA target site mapping in PRKG1 coding region, miR-20a overexpression/inhibition, cell proliferation/migration assays, hypoxia cell model FEBS Letters Medium 25447536
2003 PKG-1 expression and activity are approximately two-fold upregulated in the pulmonary vasculature of chronically hypoxic rats, localized specifically to the vasculature by quantitative immunohistochemistry. Despite this upregulation, vasodilatory responses to 8-BrcGMP are attenuated after chronic hypoxia, indicating that the impaired vasodilation is not due to decreased PKG-1 expression/activity. Isolated perfused lung vasodilatory assay, Western blotting, quantitative immunohistochemistry, PKG activity assay, pharmacological PKG inhibitors (Rp-8-Br-PET-cGMPS, KT-5823) American Journal of Physiology: Lung Cellular and Molecular Physiology Medium 12765880
2024 PRKG1 (PKG1) lies downstream of sGC/cGMP signaling and upstream of PINK1 activation. Vericiguat (sGC stimulator) upregulates PRKG1, which activates PINK1 to inhibit mitochondrial dysfunction and mtDNA cytoplasmic leakage, subsequently suppressing the STING/IRF3 inflammatory pathway in doxorubicin-induced cardiotoxicity. Adeno-associated virus-mediated cardiac PRKG1 manipulation (overexpression/silencing), RNA sequencing pathway analysis, Western blotting for PINK1/STING/IRF3, cardiomyocyte mitochondrial function assays, mouse I/R model Translational Research Medium 39059761
2019 PKG (PRKG1) induces mitochondrial biogenesis in renal proximal tubule cells via a pathway requiring p38 MAPK downstream of PKG. Pharmacological PKG activation (via sGC stimulation) and specific inhibitor studies establish the sequence: sGC → cGMP → PKG → p38 → PGC-1α nuclear localization and phosphorylation. Pharmacological inhibitors of PKG and p38 in renal proximal tubule cells, in vivo l-skepinone (p38 inhibitor) treatment in mice, nuclear fractionation for phospho-PGC-1α, mitochondrial biogenesis markers American Journal of Physiology: Renal Physiology Medium 31841384
2014 PKG activity is required for heparin-induced inhibition of vascular smooth muscle cell proliferation. Chemical inhibition of PKG (Rp-8-pCPT-cGMS) and siRNA knockdown of PKG both eliminate heparin effects on BrdU incorporation, ERK activity, Elk-1 phosphorylation, and MKP-1 synthesis. Heparin transiently increases intracellular cGMP, placing PKG downstream of heparin cell-surface receptor engagement. Chemical PKG inhibitor, PKG siRNA knockdown, BrdU incorporation, ERK/Elk-1 Western blotting, MKP-1 immunoblotting, cGMP ELISA in vascular smooth muscle cells Journal of Cellular Physiology Medium 24911927
2020 MASTL-ENSA/ARPP19-PP2A cell cycle checkpoint pathway is present and functional in anucleate human platelets. PKG (activated by cGMP-elevating agents including NO donors and riociguat) phosphorylates ENSA at S109 and ARPP19 at S104, as validated with recombinant PKG and phospho-mutants. These PKG phosphorylation sites are distinct from the MASTL-targeted S67/S62 sites. Proteomics in human platelets, recombinant MASTL/PKA/PKG kinase assays with recombinant ENSA/ARPP19 and phospho-mutants, pharmacological activation (iloprost, NO donors, riociguat, okadaic acid) Cells Medium 32085646

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1987 Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 405 3453121
1987 Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter. Gene 350 3440520
1990 Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spermatogenesis. Nucleic acids research 226 1690874
2013 Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. American journal of human genetics 195 23910461
1987 The testis-specific phosphoglycerate kinase gene pgk-2 is a recruited retroposon. Molecular and cellular biology 171 2823118
2017 Plasma Membrane Association by N-Acylation Governs PKG Function in Toxoplasma gondii. mBio 153 28465425
2002 In vitro production and nuclear transfer affect dosage compensation of the X-linked gene transcripts G6PD, PGK, and Xist in preimplantation bovine embryos. Biology of reproduction 141 11751274
1992 Differential transcription of Pgk genes during spermatogenesis in the mouse. Developmental biology 136 1426623
1986 Efficient expression of the Saccharomyces cerevisiae PGK gene depends on an upstream activation sequence but does not require TATA sequences. Molecular and cellular biology 129 3540610
1977 Electrophoretic variation for x-chromosome-linked phosphoglycerate kinase (pgk-1) in the mouse. Genetics 121 17248765
1991 X-chromosome inactivation patterns using HPRT and PGK polymorphisms in haematologically normal and post-chemotherapy females. British journal of haematology 118 1958476
2019 PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress. Nature 114 30700906
1989 Transcriptional control of the Saccharomyces cerevisiae PGK gene by RAP1. Molecular and cellular biology 112 2685568
1997 Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1). Genomics 103 9192852
2015 The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism. British journal of pharmacology 102 25297462
2020 Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway. PLoS biology 98 33186350
2019 Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice. Clinical science (London, England : 1979) 91 31337673
2017 Crosstalk between PKA and PKG controls pH-dependent host cell egress of Toxoplasma gondii. The EMBO journal 83 29030485
2001 Bidirectional transcriptional activity of PGK-neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice. Genesis (New York, N.Y. : 2000) 82 11536432
2023 NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways. Science advances 75 37531438
2005 Characterization of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG): antiparasitic activity of a PKG inhibitor. Molecular and biochemical parasitology 73 16325279
2004 Activity of cGMP-dependent protein kinase (PKG) affects sucrose responsiveness and habituation in Drosophila melanogaster. Learning & memory (Cold Spring Harbor, N.Y.) 73 15169860
1991 Determining transcript number using the polymerase chain reaction: Pgk-2, mP2, and PGK-2 transgene mRNA levels during spermatogenesis. Nucleic acids research 73 2027764
2020 Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity. Cell chemical biology 72 32359426
2012 cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function. Nature medicine 72 22270721
2014 Human exosomal placenta-associated miR-517a-3p modulates the expression of PRKG1 mRNA in Jurkat cells. Biology of reproduction 70 25273530
2016 Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways. Scientific reports 66 27581840
2010 PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4. Oncogene 63 20348951
2022 Cyclic GMP and PKG Signaling in Heart Failure. Frontiers in pharmacology 62 35479330
2018 cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway. Basic research in cardiology 62 29766323
2007 PGK deficiency. British journal of haematology 61 17222195
2007 NO mobilizes intracellular Zn2+ via cGMP/PKG signaling pathway and prevents mitochondrial oxidant damage in cardiomyocytes. Cardiovascular research 61 17570352
1990 Limited bidirectional activity of two housekeeping gene promoters: human HPRT and PGK. Gene 59 2347494
1992 Protein-DNA interactions associated with the onset of testis-specific expression of the mammalian Pgk-2 gene. Molecular and cellular biology 58 1549104
1986 Transcription and processing signals in the 3-phosphoglycerate kinase (PGK) gene from Aspergillus nidulans. Gene 58 3533726
2020 The NO-cGMP-PKG pathway in skeletal remodeling. Annals of the New York Academy of Sciences 51 32860248
2012 Phosphodiesterase-2 inhibitor reverses corticosterone-induced neurotoxicity and related behavioural changes via cGMP/PKG dependent pathway. The international journal of neuropsychopharmacology 49 22850435
2022 The Role of NO/sGC/cGMP/PKG Signaling Pathway in Regulation of Platelet Function. Cells 48 36429131
2011 IRAG and novel PKG targeting in the cardiovascular system. American journal of physiology. Heart and circulatory physiology 48 21666108
2015 Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG). The Journal of biological chemistry 47 26370085
2013 cGMP-dependent protein kinase (PKG) mediates the anticontractile capacity of perivascular adipose tissue. Cardiovascular research 43 24095868
1990 Molecular evolution of the human Pgk-2 retroposon. Nucleic acids research 43 2156237
2024 Bifidobacterium pseudolongum-Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP-PKG-mTORC1 Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 42 39308187
2022 The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders. Journal of thrombosis and haemostasis : JTH 42 35950928
2017 A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus. Molecular psychiatry 41 28265120
2023 The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies. Aging and disease 40 36818566
1985 Molecular cloning of the 3-phosphoglycerate kinase (PGK) gene from Aspergillus nidulans. Current genetics 39 3916724
1989 Characterization of the transcriptional potency of sub-elements of the UAS of the yeast PGK gene in a PGK mini-promoter. Nucleic acids research 38 2685757
2021 Gastrodin promotes hippocampal neurogenesis via PDE9-cGMP-PKG pathway in mice following cerebral ischemia. Neurochemistry international 36 34419525
1993 A factor stimulating transcription of the testis-specific Pgk-2 gene recognizes a sequence similar to the binding site for a transcription inhibitor of the somatic-type Pgk-1 gene. Nucleic acids research 36 8441629
2019 Self-regulation and the foraging gene (PRKG1) in humans. Proceedings of the National Academy of Sciences of the United States of America 34 30782798
2016 Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation. Structure (London, England : 1993) 34 27066748
2007 Cardioprotection: spotlight on PKG. British journal of pharmacology 33 17876305
2023 Semaglutide inhibits ischemia/reperfusion-induced cardiomyocyte apoptosis through activating PKG/PKCε/ERK1/2 pathway. Biochemical and biophysical research communications 32 36706596
1998 The EIIGlc protein is involved in glucose-mediated activation of Escherichia coli gapA and gapB-pgk transcription. Journal of bacteriology 32 9851989
2018 Prevention of PKG-1α Oxidation Suppresses Antihypertrophic/Antifibrotic Effects From PDE5 Inhibition but not sGC Stimulation. Circulation. Heart failure 31 29545395
2003 Pulmonary PKG-1 is upregulated following chronic hypoxia. American journal of physiology. Lung cellular and molecular physiology 30 12765880
2022 Phosphatidic acid suppresses autophagy through competitive inhibition by binding GAPC (glyceraldehyde-3-phosphate dehydrogenase) and PGK (phosphoglycerate kinase) proteins. Autophagy 29 35289711
2019 Propranolol selectively inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 30841438
2021 The novel ZEB1-upregulated protein PRTG induced by Helicobacter pylori infection promotes gastric carcinogenesis through the cGMP/PKG signaling pathway. Cell death & disease 27 33542225
2016 PRKG1 and genetic diagnosis of early-onset thoracic aortic disease. European journal of clinical investigation 27 27442293
2007 Association of VASP with TRPC4 in PKG-mediated inhibition of the store-operated calcium response in mesangial cells. American journal of physiology. Renal physiology 27 17913834
2017 Augmentation of cGMP/PKG pathway and colonic motility by hydrogen sulfide. American journal of physiology. Gastrointestinal and liver physiology 25 28705807
2012 Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I): pathophysiological significance. Cardiovascular research 25 23139241
1991 Timing of paternal Pgk-1 expression in embryos of transgenic mice. Development (Cambridge, England) 25 1879353
2021 Current trends and future perspectives for heart failure treatment leveraging cGMP modifiers and the practical effector PKG. Journal of cardiology 24 33814252
2020 The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets. Cells 23 32085646
2019 Elucidation of cGMP-dependent induction of mitochondrial biogenesis through PKG and p38 MAPK in the kidney. American journal of physiology. Renal physiology 23 31841384
2018 cGMP/PKG-I Pathway-Mediated GLUT1/4 Regulation by NO in Female Rat Granulosa Cells. Endocrinology 23 29300939
2016 Helional induces Ca2+ decrease and serotonin secretion of QGP-1 cells via a PKG-mediated pathway. Journal of molecular endocrinology 23 27553203
2014 Heparin responses in vascular smooth muscle cells involve cGMP-dependent protein kinase (PKG). Journal of cellular physiology 23 24911927
2024 Isthmin-1 alleviates cardiac ischaemia/reperfusion injury through cGMP-PKG signalling pathway. Cardiovascular research 21 38637328
2022 Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration. Cell death discovery 21 35241647
2022 Chronological attenuation of NPRA/PKG/AMPK signaling promotes vascular aging and elevates blood pressure. Aging cell 21 36016499
2015 Hydrogen sulfide mediates the cardioprotective effects of gene therapy with PKG-Iα. Basic research in cardiology 21 26036467
2014 MiR-20a regulates the PRKG1 gene by targeting its coding region in pulmonary arterial smooth muscle cells. FEBS letters 21 25447536
2017 The bradykinin-cGMP-PKG pathway augments insulin sensitivity via upregulation of MAPK phosphatase-5 and inhibition of JNK. American journal of physiology. Endocrinology and metabolism 20 28679626
2012 A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to acute oxidative stress at the Drosophila larval neuromuscular junction. Journal of neurophysiology 20 23136350
1994 Clonal determination by the fragile X (FMR1) and phosphoglycerate kinase (PGK) genes in hematological malignancies. Cancer research 20 7923142
2022 Corallodiscus flabellata B. L. Burtt extract and isonuomioside A ameliorate Aβ25-35-induced brain injury by inhibiting apoptosis, oxidative stress, and autophagy via the NMDAR2B/CamK Ⅱ/PKG pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 35489325
2020 Empagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels. Toxicology and applied pharmacology 19 32717242
2019 The natural history of type B aortic dissection in patients with PRKG1 mutation c.530G>A (p.Arg177Gln). Journal of vascular surgery 19 30871887
2019 Vasodilatory effect of kaempferol-7-O-α-L-rhamnopyranoside via NO-cGMP-PKG signaling. Archives of biochemistry and biophysics 19 30981710
2015 Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability. Biochemistry 19 26132214
1989 Cloning and characterization of the Escherichia coli phosphoglycerate kinase (pgk) gene. Gene 19 2545537
1995 Molecular genetic heterogeneity of phosphoglycerate kinase (PGK) deficiency. Muscle & nerve. Supplement 18 7603527
2021 Emodin Interferes With Nitroglycerin-Induced Migraine in Rats Through CGMP-PKG Pathway. Frontiers in pharmacology 17 34744735
2020 Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway. Frontiers in pharmacology 17 33013408
2015 Hydrogen sulfide and PKG in ischemia-reperfusion injury: sources, signaling, accelerators and brakes. Basic research in cardiology 17 26318600
2015 PKC and AKT Modulate cGMP/PKG Signaling Pathway on Platelet Aggregation in Experimental Sepsis. PloS one 17 26375024
1989 Differential expression of gap and pgk genes within the gap operon of Zymomonas mobilis. Journal of bacteriology 17 2687242
2024 Vericiguat attenuates doxorubicin-induced cardiotoxicity through the PRKG1/PINK1/STING axis. Translational research : the journal of laboratory and clinical medicine 16 39059761
2019 A post-GWAS confirming effects of PRKG1 gene on milk fatty acids in a Chinese Holstein dairy population. BMC genetics 16 31269900
1994 The yeast protein Gcr1p binds to the PGK UAS and contributes to the activation of transcription of the PGK gene. Molecular & general genetics : MGG 16 7808400
2019 Genes of the cGMP-PKG-Ca2+ signaling pathway are alternatively spliced in cardiomyopathy: Role of RBFOX2. Biochimica et biophysica acta. Molecular basis of disease 15 31778749
2024 Chronic circadian rhythm disorder induces heart failure with preserved ejection fraction-like phenotype through the Clock-sGC-cGMP-PKG1 signaling pathway. Scientific reports 14 38734687
2022 A G-Protein-Coupled Receptor Modulates Gametogenesis via PKG-Mediated Signaling Cascade in Plasmodium berghei. Microbiology spectrum 14 35404079
2022 Prenatal chronic stress impairs the learning and memory ability via inhibition of the NO/cGMP/PKG pathway in the Hippocampus of offspring. Behavioural brain research 14 35850398
2007 Sodium nitroprusside activates p38 mitogen activated protein kinase through a cGMP/PKG independent mechanism. Life sciences 14 17707440
2016 The Drosophila foraging gene human orthologue PRKG1 predicts individual differences in the effects of early adversity on maternal sensitivity. Cognitive development 13 28827895

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