Affinage

PRKACA

cAMP-dependent protein kinase catalytic subunit alpha · UniProt P17612

Length
351 aa
Mass
40.6 kDa
Annotated
2026-06-10
67 papers in source corpus 20 papers cited in narrative 22 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

PRKACA encodes the catalytic α subunit (Cα) of cAMP-dependent protein kinase A, a serine/threonine kinase whose activity is normally restrained by binding to PRKAR regulatory subunits; releasing this restraint converts PRKACA into a constitutive driver of endocrine and oncogenic phenotypes (PMID:24747643, PMID:24700472). Activating point mutations cluster in the P+1 loop of the catalytic subunit—most prominently L205R/L206R—and act by disrupting the interaction with the PRKAR1A regulatory subunit, producing autonomous kinase activity, increased substrate phosphorylation, and downstream target gene expression that drives adrenal adenoma and Cushing's syndrome (PMID:24747643, PMID:24700472, PMID:40504162); in-frame microinsertions in exons 7–8 similarly abolish PRKAR1A binding in cardiac myxoma (PMID:28369983), and loss of PRKAR1A itself provides an alternative route to PKA deregulation (PMID:29222914). The DNAJB1-PRKACA fusion, created by a ~400-kb chromosome 19 deletion that joins the DNAJB1 J-domain to the PRKACA catalytic domain, retains kinase activity and is both necessary and sufficient to drive fibrolamellar hepatocellular carcinoma, with continued expression required for tumor maintenance (oncogene addiction) (PMID:24578576, PMID:29162699, PMID:28923495, PMID:36302174); the fusion phosphorylates an overlapping but distinct substrate set relative to wild-type Cα and reprograms transcription through SIK inactivation and CRTC2-p300 signaling (PMID:39326063, PMID:34436901). Beyond these oncogenic contexts, PRKACA phosphorylates specific substrates to control discrete cellular programs: BAD to enable BCL-XL survival signaling under HER2 inhibition (PMID:24909179), MORC2-Thr582 to protect it from chaperone-mediated autophagy and confer antiestrogen resistance downstream of GPER1 (PMID:32401166), and CDC25B-Ser321 to regulate the G2/M transition (PMID:18633139). Germline PRKACA variants that increase cAMP sensitivity and inhibit hedgehog signaling cause a developmental syndrome with septal and skeletal defects (PMID:33058759). The fusion junction itself is processed and presented as an HLA-restricted neoantigen, establishing an immunotherapeutic axis (PMID:36302754).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Establishing the chromosomal position of the PKA catalytic α subunit gene provided the genomic anchor later required to interpret rearrangements and copy-number events at this locus.

    Evidence PCR, Southern blot, somatic cell hybrid mapping and two-color FISH localizing PRKACA to 19p13.1

    PMID:8884279

    Open questions at the time
    • Does not address kinase function or regulation
    • No link to disease at this stage
  2. 2008 Medium

    Identifying CDC25B-Ser321 as a PRKACA phosphorylation site explained how cAMP/PKA imposes G2 arrest, linking the kinase to direct cell-cycle control.

    Evidence Microinjection of CDC25B mutants, phospho-Ser321 Western blot, and MPF activation assay in mouse fertilized eggs

    PMID:18633139

    Open questions at the time
    • Demonstrated in oocyte/embryo system, generality to somatic cells untested
    • Single lab
  3. 2014 High

    Discovery of the DNAJB1-PRKACA chimeric transcript answered what genetic lesion defines fibrolamellar HCC and showed the fusion retains kinase activity.

    Evidence RNA-seq, RT-PCR, immunoprecipitation, Western blot and cell-based kinase assay on FL-HCC tumor tissue

    PMID:24578576

    Open questions at the time
    • Did not prove the fusion is sufficient to cause tumors
    • Downstream substrate program undefined
  4. 2014 High

    The L205R/L206R substitution was shown to disrupt PRKAR1A binding and produce constitutive activity, defining the molecular basis of cortisol-producing adrenal adenomas.

    Evidence Exome/RNA sequencing plus in vitro kinase and PRKAR1A-binding assays

    PMID:24700472 PMID:24747643

    Open questions at the time
    • Full downstream substrate set not mapped at this stage
    • Structural mechanism of disruption inferred from mutation location
  5. 2014 Medium

    A kinase ORF screen revealed PRKACA promotes survival under HER2 inhibition through BAD inactivation rather than MAPK/PI3K restoration, defining a distinct PKA survival axis.

    Evidence Kinase ORF screen, pharmacological BCL-XL/BCL-2 blockade, MAPK/PI3K readouts in HER2-amplified breast cancer cells

    PMID:24909179

    Open questions at the time
    • Direct phosphorylation of BAD by PRKACA not biochemically isolated here
    • Single lab
  6. 2017 High

    In vivo modeling answered whether the fusion is causal: endogenous DNAJB1-PRKACA, but not wild-type PRKACA overexpression, was sufficient to drive FL-HCC-like tumors in mice.

    Evidence CRISPR/Cas9 genome editing and hydrodynamic somatic gene transfer in mouse liver with histology, IHC, RNA-seq, WES

    PMID:28923495 PMID:29162699

    Open questions at the time
    • Mechanistic distinction between fusion and wild-type signaling not yet resolved
    • β-catenin cooperation noted but not fully dissected
  7. 2017 Medium

    PRKACA microinsertions in cardiac myxoma were shown to abolish PRKAR1A binding, extending the loss-of-regulation mechanism beyond point mutations to another tumor type.

    Evidence Sanger sequencing with functional PRKAR1A-interaction and PKA pathway activation assays

    PMID:28369983

    Open questions at the time
    • Single lab
    • Downstream substrate consequences not characterized
  8. 2018 Medium

    Structural studies addressed how the J-domain affects the chimeric kinase, finding it adopts an ensemble of conformations without obvious steric clash with holoenzyme components.

    Evidence NMR spectroscopy and molecular dynamics simulations of the DNAJB1-PRKACA chimera

    PMID:29335433

    Open questions at the time
    • Functional consequence of J-domain conformations on substrate selection unresolved
    • Single lab, computational/biophysical only
  9. 2018 Medium

    PRKAR1A loss in Carney complex patients was shown to cause FL-HCC, establishing an alternative route to PKA deregulation independent of the fusion.

    Evidence FISH (negative for PRKACA rearrangement), PRKAR1A sequencing and IHC showing protein loss

    PMID:29222914

    Open questions at the time
    • Single lab
    • Does not establish identical downstream program as the fusion
  10. 2019 Medium

    Identifying MORC2-Thr582 as a PRKACA substrate downstream of GPER1 linked the kinase to autophagy escape and antiestrogen resistance in breast cancer.

    Evidence Knockdown/overexpression, T582A phospho-dead mutant, co-IP and proliferation assays

    PMID:32401166

    Open questions at the time
    • Single lab
    • Direct kinase-substrate biochemistry vs cellular correlation
  11. 2020 Medium

    Germline PRKACA variants were shown to raise cAMP sensitivity and inhibit hedgehog signaling, providing a mechanism for a multisystem developmental disorder.

    Evidence Computational structural analysis, cAMP-sensitivity assays and hedgehog reporter assays in NIH 3T3 cells

    PMID:33058759

    Open questions at the time
    • Mechanism linking PKA to hedgehog suppression not fully delineated
    • Single lab
  12. 2021 Medium

    Phosphoproteomics defined the direct substrate landscape of wild-type versus chimeric PRKACA, showing overlapping but distinct targets and some inhibitor-resistant substrates.

    Evidence Cell-based and in vitro phosphoproteomics with recombinant enzymes and PKA inhibitors, mass spectrometry

    PMID:34436901

    Open questions at the time
    • Functional importance of individual differential substrates not validated
    • Single lab
  13. 2022 Medium

    Demonstrating that the fusion junction is processed into HLA-presented neoantigens that elicit T cell responses opened an immunotherapeutic strategy against FL-HCC.

    Evidence Mass spectrometry immunopeptidomics, T cell functional assays and single-cell TCR sequencing

    PMID:36302754

    Open questions at the time
    • Clinical efficacy not established
    • Single institution
  14. 2023 Medium

    shRNA depletion in PDX models established oncogene addiction, showing continued fusion expression is required for tumor maintenance and selectively lethal to fusion-positive cells.

    Evidence shRNA knockdown and patient-derived xenograft models in vivo with viability assays

    PMID:36302174

    Open questions at the time
    • Mechanism of cell death upon fusion loss not detailed
    • Single lab
  15. 2025 Medium

    SIK inactivation and CRTC2-p300 transcriptional reprogramming were identified as a downstream axis through which the fusion drives FL-HCC growth.

    Evidence Functional model-system studies and human tumor specimen analysis with pathway dissection

    PMID:39326063

    Open questions at the time
    • Relative contribution versus other fusion substrates unquantified
    • Single lab
  16. 2025 Medium

    MD/network analysis of the Cushing's L205R mutation revealed both local P+1 pocket disruption and long-range allosteric effects on the phosphoryl-transfer site, refining the mechanism of altered specificity.

    Evidence Molecular dynamics simulations, protein residue network analysis and crystal-structure comparison

    PMID:40504162

    Open questions at the time
    • No experimental mutagenesis validation of predicted allosteric effects
    • Some distal changes not captured in crystal structure
  17. 2025 Medium

    An upstream regulatory layer was uncovered: Nsun2-mediated m5C methylation of PRKACA mRNA promotes its translation and PKA activity, with functional consequences for cardiac contractility and hypertrophy.

    Evidence m5C-RIP-seq, RNA pulldown, polysome profiling, cardiac-specific KO and rAAV9 overexpression with calcium and contraction measurements

    PMID:39990213

    Open questions at the time
    • Generality beyond cardiac tissue untested
    • Single lab
  18. 2025 Medium

    A fusion-specific peptide degrader combined with siRNA achieved selective elimination of DNAJB1::PRKACA without affecting native PRKACA, demonstrating a tractable therapeutic vulnerability.

    Evidence mRNA-delivered peptide degrader plus siRNA in FLC cell and PDX models with selectivity controls (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Clinical translation untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the J-domain conformational ensemble mechanistically rewires substrate selection and confers oncogenic, inhibitor-resistant signaling distinct from wild-type Cα remains unresolved.
  • No structural model linking J-domain position to differential substrate phosphorylation
  • Functional roles of fusion-specific substrates not validated in tumor maintenance

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 4 GO:0140657 ATP-dependent activity 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1640170 Cell Cycle 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
BADCDC25BDNAJB1GPER1MORC2NSUN2PRKAR1A
Complex memberships
PKA holoenzyme

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 A ~400-kb deletion on chromosome 19 creates a chimeric DNAJB1-PRKACA transcript encoding a fusion protein containing the DNAJB1 J-domain fused in-frame to the PRKACA catalytic domain; immunoprecipitation and Western blot confirmed expression in FL-HCC tumor tissue, and cell culture assay demonstrated the fusion protein retains kinase activity. RNA sequencing, RT-PCR, immunoprecipitation, Western blot, cell-based kinase assay Science High 24578576
2014 Somatic PRKACA p.Leu206Arg (L206R) substitution directly disrupts interaction with the regulatory subunit PRKAR1A, causing constitutive catalytic activity, increased phosphorylation of downstream PKA targets, and autonomous cortisol production driving adrenal adenoma development. Exome sequencing, in vitro kinase/binding assays, functional characterization of PRKAR1A binding loss Nature genetics High 24700472 24747643
2014 The PRKACA L205R/L206R mutation locates in the P+1 loop of the PKA catalytic subunit, promotes PKA substrate phosphorylation and downstream target gene expression, conferring constitutive kinase activity. Whole-exome sequencing, RNA sequencing, in vitro phosphorylation assays Science High 24700472 24747643
2017 Expression of the endogenous DNAJB1-PRKACA fusion protein (but not overexpression of wild-type PRKACA alone) in mouse liver via CRISPR-Cas9 is sufficient to drive formation of tumors resembling FL-HCC, establishing the fusion as an oncogenic driver beyond simple PRKACA overexpression; tumorigenesis is significantly enhanced by β-catenin activation. CRISPR/Cas9 genome editing, somatic gene transfer, histology, IHC, RNA sequencing, whole-exome sequencing Proceedings of the National Academy of Sciences High 28923495 29162699
2017 CRISPR/Cas9-induced Dnajb1-Prkaca fusion gene in wild-type mice is sufficient to initiate liver tumor formation with FL-HCC features in the absence of other genetic alterations or carcinogens, confirming the fusion as a standalone oncogenic driver. CRISPR/Cas9 hydrodynamic tail-vein injection, histology, IHC, RNA sequencing, whole-exome sequencing Gastroenterology High 28923495
2017 PRKACA microinsertions (in-frame, 18-33 bp) in exons 7 and 8 cause the mutant PRKACA protein to lose binding to PRKAR1A regulatory subunit, leading to constitutive PKA pathway activation in sporadic cardiac myxoma. Sanger sequencing, functional binding assays (PRKAR1A interaction loss), PKA pathway activation assays The Journal of pathology Medium 28369983
2018 NMR and molecular dynamics simulations of the DNAJB1-PRKACA chimeric kinase reveal an ensemble of conformations in which the J-domain can be tucked under the large lobe or swing free in solution, with no obvious steric interaction with RIIβ holoenzyme components. Molecular dynamics simulations, NMR spectroscopy, structural modeling Scientific reports Medium 29335433
2018 Loss of PRKAR1A (regulatory subunit of PKA) expression due to inactivating PRKAR1A mutations in Carney complex patients leads to PKA activation and fibrolamellar carcinoma formation, providing an alternative mechanism to DNAJB1-PRKACA fusion for PKA deregulation in FL-HCC. FISH (negative for PRKACA rearrangement), PRKAR1A sequencing, IHC (loss of PRKAR1A protein) Hepatology Medium 29222914
2019 GPER1 (G protein-coupled estrogen receptor 1) activates PRKACA, which in turn phosphorylates MORC2 at threonine 582, protecting MORC2 from chaperone-mediated autophagy (CMA)-mediated lysosomal degradation and contributing to estrogen-induced cell proliferation and antiestrogen resistance in breast cancer cells. Knockdown/overexpression, phosphorylation-deficient mutant (T582A), co-immunoprecipitation, functional cell proliferation assays Autophagy Medium 32401166
2014 PRKACA expression rescues HER2-amplified breast cancer cells from HER2 inhibition not by restoring MAPK or PI3K signaling, but by inactivating the pro-apoptotic protein BAD, permitting survival signaling through BCL-XL. Kinase ORF screen, pharmacological BCL-XL/BCL-2 blockade, signaling pathway analysis (MAPK, PI3K readouts negative) Oncogene Medium 24909179
2020 Germline or mosaic missense variants in PRKACA produce PKA holoenzymes that are more sensitive to cAMP activation than wild-type, and expression of PRKACA variants inhibits hedgehog signaling in NIH 3T3 fibroblasts, providing a mechanism for the developmental defects (atrioventricular septal defects, polydactyly, skeletal/ectodermal abnormalities) observed in affected individuals. Computational structural analysis, cAMP-sensitivity assays, hedgehog signaling reporter assays in NIH 3T3 cells American journal of human genetics Medium 33058759
2008 PRKACA regulates G2/M transition in mouse fertilized eggs by phosphorylating CDC25B at Ser321 (but not Ser229); unphosphorylatable CDC25B-S321A mutant overrides G2 arrest even under elevated cAMP by directly dephosphorylating CDC2A-Tyr15 to activate MPF. Microinjection of CDC25B mutants, Western blot with phospho-Ser321 antibody, MPF activation assay, cAMP treatment Biology of reproduction Medium 18633139
2023 Continued DNAJB1-PRKACA expression is required not only for FL-HCC tumor maintenance but its inhibition causes tumor cell death (oncogene addiction); shRNA-mediated knockdown of the fusion in patient-derived xenografts inhibits tumor growth in vivo with no effect on hepatocellular carcinoma cells not expressing the fusion. shRNA knockdown, patient-derived xenograft (PDX) models in vivo, cell viability assays Clinical cancer research Medium 36302174
2025 DNAJB1-PRKACA fusion drives FL-HCC through inactivation of SIK (salt-inducible kinase), which stimulates CRTC2-p300-mediated transcriptional reprogramming to drive tumor growth. Functional studies in model systems, examination of human tumor specimens, pathway analysis Cancer discovery Medium 39326063
2025 Nsun2 methylates PRKACA mRNA at specific sites, promoting PRKACA translation in a YBX1-dependent manner; cardiac-specific Nsun2 knockout markedly reduces PKA activity, impairs substrate phosphorylation, myocyte contraction/relaxation, and calcium transients, while Nsun2 overexpression sensitizes the heart to hypertrophic stimuli in a PRKACA-dependent manner. m5C-RIP-seq, RNA pulldown, polysome profiling, cardiac-specific KO (Cre/LoxP), rAAV9 overexpression, IonOptix calcium measurement, reporter gene analysis Theranostics Medium 39990213
1996 The PRKACA gene encoding the catalytic subunit Cα of cAMP-dependent protein kinase was localized to human chromosome region 19p13.1 by PCR and Southern blot analysis of somatic cell hybrid mapping panels, confirmed by two-color FISH. PCR, Southern blot, somatic cell hybrid panel, two-color FISH Genomics High 8884279
2021 Integrated cell-based and in vitro phosphoproteomics identified direct substrates of PRKACA and the DNAJB1-PRKACA chimeric kinase, revealing the chimera targets overlapping but distinct substrate sets and altered pathways compared to wild-type PRKACA, with some substrates persisting under PKA inhibitor treatment. Cell-based phosphoproteomics, in vitro rephosphorylation with recombinant enzymes, PKA inhibitor treatment (rpcAMPs and PKI), mass spectrometry Journal of proteome research Medium 34436901
2025 The PRKACA L205R Cushing's syndrome mutation locally disrupts the P+1 hydrophobic pocket (displacing the P+1-residue and altering substrate specificity) and has long-range allosteric effects on the linker connecting the A helix to β strand 1 and on the phosphoryl transfer site, as revealed by MD simulations and protein residue network analysis; some distal changes are not captured in the crystal structure. Molecular dynamics simulations, protein residue network (LSP) analysis, crystal structure comparison Proceedings of the National Academy of Sciences Medium 40504162
2025 A fusion-protein-specific peptide degrader selectively eliminates DNAJB1::PRKACA (and ATP1B1::PRKACA) without affecting native PRKACA; specificity reflects structural properties of the fusion. Combining the degrader with siRNA against the fusion transcript in a single mRNA accelerates degradation and is lethal to FLC tumor cells in preclinical models with no toxicity to non-FLC cells. mRNA-delivered peptide degrader, siRNA combination, FLC cell/PDX models in vitro and in vivo, selectivity controls bioRxivpreprint Medium
2025 PRKACA (PKA catalytic α subunit) phosphorylates huntingtin at S421 (pS421-HTT) in human cells, as demonstrated by an ultrasensitive immunoassay showing that PRKACA activity regulates endogenous S421-HTT phosphorylation levels. Ultrasensitive immunoassay, cell-based PRKACA activity modulation, endogenous pS421-HTT detection bioRxivpreprint Low
2016 Functional analysis of the novel PRKACA p.His88Asp variant found in an aldosterone-producing adenoma showed it was NOT associated with gain of function (negative finding), distinguishing it mechanistically from the p.Leu206Arg gain-of-function mutation. In vitro enzymatic activity assay of PRKACA variants, immunofluorescence for CYP11B2/CYP11B1 The Journal of clinical endocrinology and metabolism Medium 27270477
2022 DNAJB1-PRKACA-derived HLA class I and class II ligands are naturally processed and presented on tumor cells as confirmed by mass spectrometry-based immunopeptidome analysis, and induce multifunctional cytotoxic CD8+ and T-helper 1 CD4+ T cell responses, establishing the fusion junction as a bona fide neoantigen. Mass spectrometry immunopeptidome analysis, T cell functional assays, single-cell RNA sequencing of TCRs Nature communications Medium 36302754

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science (New York, N.Y.) 390 24578576
2014 Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. Nature genetics 187 24747643
2014 Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. Science (New York, N.Y.) 179 24700472
2015 Protein kinase A catalytic subunit isoform PRKACA; History, function and physiology. Gene 162 26687711
2017 DNAJB1-PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America 139 29162699
2019 Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct. Gastroenterology 131 31678302
2015 DNAJB1-PRKACA is specific for fibrolamellar carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 128 25698061
2019 DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 104 31676785
2017 CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma. Gastroenterology 87 28923495
2014 PRKACA mediates resistance to HER2-targeted therapy in breast cancer cells and restores anti-apoptotic signaling. Oncogene 87 24909179
2016 Genetic Landscape of Sporadic Unilateral Adrenocortical Adenomas Without PRKACA p.Leu206Arg Mutation. The Journal of clinical endocrinology and metabolism 69 27389594
2022 The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma. Nature communications 56 36302754
2015 PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study of 60 cases. European journal of endocrinology 56 25750087
2019 Stabilization of MORC2 by estrogen and antiestrogens through GPER1- PRKACA-CMA pathway contributes to estrogen-induced proliferation and endocrine resistance of breast cancer cells. Autophagy 55 32401166
2018 Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the classic DNAJB1-PRKACA fusion. Hepatology (Baltimore, Md.) 53 29222914
2015 PRKACA: the catalytic subunit of protein kinase A and adrenocortical tumors. Frontiers in cell and developmental biology 50 26042218
2014 Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes. Human pathology 43 25449630
2020 Germline and Mosaic Variants in PRKACA and PRKACB Cause a Multiple Congenital Malformation Syndrome. American journal of human genetics 42 33058759
2015 Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations. European journal of endocrinology 39 25924874
2016 PRKACA Somatic Mutations Are Rare Findings in Aldosterone-Producing Adenomas. The Journal of clinical endocrinology and metabolism 36 27270477
2016 Double adrenocortical adenomas harboring independent KCNJ5 and PRKACA somatic mutations. European journal of endocrinology 34 27165862
2014 Somatic mutations of the catalytic subunit of cyclic AMP-dependent protein kinase (PRKACA) gene in Japanese patients with several adrenal adenomas secreting cortisol [Rapid Communication]. Endocrine journal 28 25069672
2023 Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA. Clinical cancer research : an official journal of the American Association for Cancer Research 26 36302174
2018 Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for Fibrolamellar Hepatocellular Carcinoma. Scientific reports 21 29335433
2018 Cyclic AMP-dependent protein kinase catalytic subunit A (PRKACA): the expected, the unexpected, and what might be next. The Journal of pathology 17 29205368
1996 The gene encoding the catalytic subunit C alpha of cAMP-dependent protein kinase (locus PRKACA) localizes to human chromosome region 19p13.1. Genomics 17 8884279
2025 DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming. Cancer discovery 16 39326063
2023 Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 16 37871652
2022 Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems. Virchows Archiv : an international journal of pathology 16 36152045
2024 DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma. Cell reports. Medicine 15 38508137
2017 Microinsertions in PRKACA cause activation of the protein kinase A pathway in cardiac myxoma. The Journal of pathology 15 28369983
2008 CDC25B acts as a potential target of PRKACA in fertilized mouse eggs. Biology of reproduction 14 18633139
2024 FusionVAC22_01: a phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion. Frontiers in oncology 13 38606105
2022 Novel protein kinase cAMP-Activated Catalytic Subunit Alpha (PRKACA) inhibitor shows anti-tumor activity in a fibrolamellar hepatocellular carcinoma model. Biochemical and biophysical research communications 13 35839742
2025 Nsun2 controls cardiac homeostasis and hypertrophic response by regulating PRKACA expression. Theranostics 12 39990213
2024 DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma. PLoS genetics 12 38512964
2023 GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 12 37980543
2016 PRKACA Mutations in Adrenal Adenomas: Genotype/Phenotype Correlations. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 12 27871112
2016 Clinical characteristics of PRKACA mutations in Chinese patients with adrenal lesions: a single-centre study. Clinical endocrinology 11 27296931
2023 Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3β Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay. Cancers 10 38201567
2021 Genotype-specific cortisol production associated with Cushing's syndrome adenoma with PRKACA mutations. Molecular and cellular endocrinology 10 34520814
2017 Lipofuscin Accumulation in Cortisol-Producing Adenomas With and Without PRKACA Mutations. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 10 28834963
2024 Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK pathway. Journal of cellular and molecular medicine 9 38856956
2024 Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway. Journal of ethnopharmacology 9 38908492
2022 DNAJB1-PRKACA in HEK293T cells induces LINC00473 overexpression that depends on PKA signaling. PloS one 9 35167623
2019 Somatic PRKACA Mutations: Association With Transition From Pituitary-Dependent to Adrenal-Dependent Cushing Syndrome. The Journal of clinical endocrinology and metabolism 8 31276155
2022 Decabromodiphenyl ether-induced PRKACA hypermethylation contributed to glycolipid metabolism disorder via regulating PKA/AMPK pathway in rat and L-02 cells. Environmental toxicology and pharmacology 6 35007761
2022 The Use of Fluorescence in situ Hybridization to Confirm PRKACA Gene Rearrangement in Fibrolamellar Hepatocellular Carcinoma: A Validation Study. Annals of clinical and laboratory science 5 35777788
2021 Integrated Phosphoproteomics for Identifying Substrates of Human Protein Kinase A (PRKACA) and Its Oncogenic Mutant DNAJB1-PRKACA. Journal of proteome research 5 34436901
2025 Expression of DNAJB1-PRKACA oncogene suppresses the differentiation potential of liver progenitor organoids towards a hepatocyte lineage. Scientific reports 4 40670531
2024 ASIC1 promotes migration and invasion of hepatocellular carcinoma via the PRKACA/AP-1 signaling pathway. Carcinogenesis 4 38306794
2024 Rare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review. BMC endocrine disorders 3 39010034
2023 Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review. Archives of endocrinology and metabolism 3 37988664
2020 DNA methylation of the prkaca gene involved in osmoregulation in tilapia hybrids (Oreochromis mossambicus × Oreochromis hornorum). Gene 3 32439378
2013 Computational prediction and characterisation of ubiquitously expressed new splice variant of Prkaca gene in mouse. Cell biology international 3 23456795
2024 Therapeutic, Clinicopathological, and Molecular Correlates of PRKACA Expression in Gastrointestinal Cancers. Pharmaceuticals (Basel, Switzerland) 2 39458904
2026 Global Re-Analysis Confirms Absence of the DNAJB1::PRKACA Fusion in Hepatoblastoma. Comment on Fleifil et al. DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways. Cancers 2025, 17, 83. Cancers 1 41827810
2025 A novel high-throughput screening platform to identify inhibitors of DNAJB1-PRKACA-driven transcriptional activity in fibrolamellar carcinoma. SLAS discovery : advancing life sciences R & D 1 39947627
2025 Local and distal changes in dynamics are caused by an L205R Cushing's syndrome mutant in PRKACA. Proceedings of the National Academy of Sciences of the United States of America 1 40504162
2021 Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients. Endocrinology and metabolism (Seoul, Korea) 1 34852451
2026 Correction: DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma. PLoS genetics 0 41746900
2026 Fusion DNAJB1::PRKACA in Non-Fibrolamellar Cancer Cases. Reply to Arif et al. Global Re-Analysis Confirms Absence of the DNAJB1::PRKACA Fusion in Hepatoblastoma. Comment on "Fleifil et al. DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways. Cancers 2025, 17, 83". Cancers 0 41899523
2026 Combined skeletal dysplasia and vasculopathy phenotypes associated with in-frame intragenic deletion in PRKACA. HGG advances 0 42157491
2026 The DNAJB1-PRKACA Oncogenic Fusion Drives Stepwise Biliary and Pancreatic Carcinogenesis from Intraductal Precursor Lesions. bioRxiv : the preprint server for biology 0 42244708
2025 A Rare Case of PRKACA Duplication-Associated Childhood-Onset Primary Pigmented Nodular Adrenocortical Disease. JCEM case reports 0 40066253
2025 Antidepressant-Like Mechanisms of Gekko gecko Active Compounds: Multi-Omics Elucidation of the cAMP-PRKACA-BDNF Signaling Axis. Chemistry & biodiversity 0 41417271
2019 DNAJB1-PRKACA-positive metastatic fibrolamellar carcinoma with unknown primary in a pediatric patient. Pediatric blood & cancer 0 31736218

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