Affinage

PRKAR1A

cAMP-dependent protein kinase type I-alpha regulatory subunit · UniProt P10644

Length
381 aa
Mass
43.0 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKAR1A encodes the type Iα regulatory subunit (RIα) of cAMP-dependent protein kinase A (PKA), functioning as the principal inhibitory constraint on PKA catalytic subunit activity and thereby serving as a tumor suppressor across multiple endocrine and non-endocrine tissues. RIα sequesters the PKA catalytic subunit Cα in an inactive holoenzyme; loss-of-function mutations—whether through nonsense-mediated mRNA decay, proteasomal degradation of aberrant proteins, or expression of dominant-negative variants that fail to bind Cα or cAMP—release constitutively active PKA-Cα, which drives tumorigenesis through compartment-specific activation of the B-Raf/MEK/ERK cascade, Wnt/β-catenin signaling, Rac1-dependent suppression of NF2/Merlin, cell cycle deregulation via E2F1/cyclin D1, and proteasomal degradation of vimentin promoting mesenchymal-to-epithelial transition (PMID:11115848, PMID:17079485, PMID:23045281, PMID:20080939, PMID:18413734). Distinct gain-of-function mutations that impair cAMP binding without destabilizing the protein instead cause hormone-resistant acrodysostosis, mechanistically separating cAMP-insensitivity from the protein instability that underlies Carney complex tumorigenesis (PMID:21651393, PMID:26405036). RIα was originally identified as the TSE1 tissue-specific extinguisher, repressing hepatocyte gene transcription by limiting CREB phosphorylation at cAMP response elements, and additionally localizes to autophagosomal membranes where it interacts with mTOR (PMID:1832337, PMID:17204847).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 High

    The identity and function of the tissue-specific extinguisher locus TSE1 were unknown; mapping and reconstitution experiments established that PRKAR1A encodes the RIα subunit of PKA and that its expression represses hepatocyte-specific transcription by reducing CREB phosphorylation at CRE sites, revealing the first gene-regulatory function of PKA's regulatory subunit.

    Evidence Concordant expression mapping, high-resolution chromosomal mapping, transfection of wild-type and cAMP-binding-mutant RIα into hepatoma cells, in vivo footprinting at CRE

    PMID:1832337 PMID:1889088

    Open questions at the time
    • Whether CRE occupancy changes are direct or mediated through additional factors
    • Whether this transcriptional repression mechanism operates outside hepatocytes
  2. 2000 High

    It was unclear whether PRKAR1A was a bona fide tumor suppressor; sequencing of 54 Carney complex kindreds revealed that inactivating germline mutations cause premature stop codons subject to nonsense-mediated mRNA decay, resulting in haploinsufficiency and establishing PRKAR1A as a tumor suppressor gene.

    Evidence Genomic sequencing, linkage analysis, quantitative mRNA analysis demonstrating NMD, immunoblot confirming absence of truncated protein across a large patient cohort

    PMID:11115848

    Open questions at the time
    • Whether haploinsufficiency alone is sufficient or second hits are needed
    • Mechanism by which reduced RIα drives specific tissue tropism of tumors
  3. 2002 High

    Whether expressed (non-NMD) PRKAR1A mutants could also drive tumorigenesis was unresolved; characterization of an exon-6-skipping splice mutant showed it produces a shorter RIα protein that activates nuclear PKA signaling, demonstrating that dominant-negative dysfunction—not just haploinsufficiency—is a second tumorigenic mechanism.

    Evidence RT-PCR, expressed mutant protein detection, in vitro nuclear PKA phosphorylation assays, LOH analysis

    PMID:12424709

    Open questions at the time
    • Whether the expressed mutant competes with wild-type RIα for holoenzyme formation
    • Full structural basis of impaired catalytic subunit binding
  4. 2003 High

    The downstream signaling consequences of PRKAR1A loss were unknown; studies in mutant lymphoblasts revealed that augmented PKA activity paradoxically increases ERK1/2 phosphorylation and cell proliferation, identifying reversal of PKA-mediated MAPK inhibition as a key oncogenic output.

    Evidence PKA enzymatic assays, immunoblot for phospho-ERK1/2, cell proliferation and metabolism assays in PRKAR1A-mutant vs. normal lymphoblasts

    PMID:12812976

    Open questions at the time
    • Which PKA substrate directly regulates ERK activation
    • Whether this mechanism is universal across PRKAR1A-mutant tumor types
  5. 2004 High

    Whether RIα haploinsufficiency alone could initiate tumorigenesis in vivo was untested; Prkar1a heterozygous knockout mice developed sarcomas and hepatocellular carcinomas without LOH, proving haploinsufficiency is tumor-predisposing but implying cooperating genetic events are needed for progression.

    Evidence Prkar1a(+/−) mouse model, tumor histopathology, LOH analysis; corroborated by antisense transgenic model showing thyroid/adrenal hyperplasia

    PMID:15371594 PMID:15591278

    Open questions at the time
    • Identity of cooperating genetic lesions
    • Whether complete biallelic loss would accelerate tumor onset in these tissues
  6. 2006 High

    The specific MAPK cascade components activated downstream of PKA in patient tissue were uncharacterized; analysis of CNC adrenocortical tissue and lymphocytes identified B-Raf/MEK/ERK and c-Myc activation (but not Akt) as the effector axis, with increased proliferation and decreased apoptosis even with monoallelic PRKAR1A loss.

    Evidence Immunoblot and IHC for phospho-ERK1/2, B-Raf, MEK1/2, c-Myc, Akt in patient adrenal tissue and PRKAR1A-mutant lymphocytes; cell cycle and apoptosis assays

    PMID:16569736 PMID:17079485

    Open questions at the time
    • Whether B-Raf is directly phosphorylated by PKA or indirectly activated
    • Contribution of other Raf family members beyond c-Raf-1 inhibition
  7. 2007 Medium

    Whether RIα functions beyond the cytosol was unknown; imaging and co-IP revealed that RIα localizes to Rab7-positive late endosomes and LC3-positive autophagosomes, where it physically interacts with mTOR, placing the PKA regulatory subunit at autophagosome maturation.

    Evidence Live-cell fluorescence imaging of tagged RIα, co-immunoprecipitation with mTOR, colocalization with LC3 and Rab7

    PMID:17204847

    Open questions at the time
    • Whether RIα-mTOR interaction modulates autophagy flux in a functionally consequential manner
    • Reciprocal validation of the RIα-mTOR interaction
    • Whether this localization is altered in PRKAR1A-mutant tumors
  8. 2007 High

    Whether complete tissue-specific Prkar1a loss causes tumors matching human CNC was untested; pituitary-specific and osteoblast-lineage KO models developed GH-secreting adenomas and bone tumors respectively, with the latter showing Wnt pathway activation, directly linking RIα loss to tissue-specific tumorigenesis via distinct downstream pathways.

    Evidence Cre-lox conditional KO in Pit1-lineage and osteoblast precursors, tumor histopathology, hormone measurements, gene expression profiling, xenograft assays

    PMID:17932105 PMID:17975024

    Open questions at the time
    • Which Wnt ligands are most critical in bone tumors
    • Whether pituitary tumors also rely on Wnt or primarily on ERK signaling
  9. 2008 High

    The mechanism by which expressed PRKAR1A mutants cause more severe phenotypes than null alleles was unclear; detailed analysis showed the exon-6-deletion mutant fails to bind Cα and distributes diffusely in the cytoplasm, raising PKA activity without compensatory type II PKA upregulation—mechanistically distinct from haploinsufficiency. Systematic domain analysis of seven expressed mutants confirmed impaired cAMP or catalytic subunit binding as the universal mechanism.

    Evidence Confocal imaging of GFP-tagged RIα variants, PKA activity assays, cAMP-binding and catalytic subunit interaction assays across seven mutants in multiple cell lines

    PMID:18241045 PMID:18451138

    Open questions at the time
    • Structural basis for why some domain mutations preferentially disrupt cAMP vs. Cα binding
    • Whether expressed mutants sequester other PKA subunits
  10. 2008 High

    The downstream effectors of PKA in Schwann cell tumorigenesis and the basis of myxoma formation were unknown; neural crest-specific Prkar1a KO revealed Rac1 activation causing posttranscriptional NF1/NF2 suppression in schwannomas, while cardiac-specific KO showed myxomatous degeneration with suppression of cardiac transcription factors (SRF, Gata4, Nkx2-5), and constitutive PKA promoted mesenchymal-to-epithelial transition through proteasomal degradation of vimentin.

    Evidence Multiple tissue-specific conditional KOs (neural crest, cardiac), signaling pathway analysis, proteasome inhibitor rescue of vimentin, electron microscopy, IHC in human CNC tissue

    PMID:18316483 PMID:18413734 PMID:18953430

    Open questions at the time
    • How PKA activates Rac1 directly
    • Whether vimentin is a direct PKA phosphorylation substrate targeting it for degradation
    • Mechanism of posttranscriptional NF1/NF2 suppression
  11. 2010 High

    Whether Wnt signaling is a primary oncogenic effector of PRKAR1A loss across tissues was not established; transcriptomic and genetic epistasis studies using Prkar1a/Trp53 and Prkar1a/Rb1 double heterozygotes identified Wnt signaling (CCND1, CTNNB1, LEF1) as the main pathway activated by cAMP dysregulation, with siRNA against Ctnnb1, E2f1, or Cdk4 blocking proliferation of PRKAR1A-mutant human adrenal cells.

    Evidence Double heterozygous mouse models with chemical carcinogenesis, whole-genome transcriptome profiling, siRNA knockdown with cell cycle analysis in human adrenal cells

    PMID:20080939

    Open questions at the time
    • Whether β-catenin is directly stabilized by PKA phosphorylation or indirectly via GSK3β
    • Relative contribution of Wnt vs. ERK pathways across different CNC tumor types
  12. 2011 High

    Which catalytic subunit isoform mediates the phenotypes of RIα loss was unknown; genetic epistasis showed that Prkaca (Cα) heterozygosity rescues cardiac lethality and suppresses schwannomas, proving that excess Cα activity is the primary effector of Prkar1a loss. Separately, proteasomal degradation was identified as an additional mechanism producing PRKAR1A haploinsufficiency for last-exon frameshift mutations escaping NMD.

    Evidence Introduction of Prkaca or Prkacb null alleles into tissue-specific Prkar1a KO mice; mutagenesis with proteasome inhibitor rescue in three cell lines

    PMID:21852354 PMID:22205709

    Open questions at the time
    • Whether Cβ has any non-redundant role in specific PRKAR1A-mutant tumor types
    • Full repertoire of protein quality control pathways acting on mutant RIα
  13. 2011 High

    Whether PRKAR1A mutations can cause gain-of-function (hormone resistance) rather than loss-of-function (tumorigenesis) was unresolved; identification of cAMP-binding-domain mutations causing acrodysostosis—with impaired PKA activation and reduced CREB phosphorylation—established a mechanistically distinct disease class from Carney complex.

    Evidence Germline mutation sequencing, clinical hormone resistance testing, in vitro PKA stimulation assays, CRE-luciferase reporter assays

    PMID:21651393 PMID:22723333

    Open questions at the time
    • Whether all acrodysostosis mutations are exclusively in cAMP-binding domains
    • Structural basis for why these mutations impair cAMP sensing without destabilizing the protein
  14. 2012 High

    The mechanism linking PKA to NF2/Merlin loss in schwannomas was incompletely understood; double KO of Prkar1a and Rac1 in Schwann cells restored Nf2 protein and suppressed tumors, proving that Rac1 is the essential intermediate between PKA activation and Merlin suppression, acting through a Pak-dependent mechanism.

    Evidence Double conditional KO (Prkar1a/Rac1) in Schwann cells, tumor incidence analysis, immunoblot for Nf2, in vitro activated-Rac1 overexpression with Pak inhibition

    PMID:23045281

    Open questions at the time
    • How PKA directly activates Rac1
    • Whether Pak phosphorylates Merlin directly or via intermediate steps
  15. 2013 High

    Whether PKA dysregulation from PRKAR1A loss is uniform across cellular compartments was unknown; FRET-based live-cell imaging revealed compartment-specific effects—increased basal and stimulated PKA at mitochondria and cytoplasm but decreased stimulus-responsive PKA at the plasma membrane—demonstrating spatially heterogeneous signaling dysregulation.

    Evidence Compartment-targeted FRET-based AKAR3 and Epac1-camps reporters in live cells with siRNA RIα knockdown, validated in patient adrenal cells

    PMID:24122441

    Open questions at the time
    • Which compartment-specific PKA targets drive tumorigenesis vs. hormone resistance
    • Role of AKAPs in directing compartment-specific RIα functions
  16. 2015 High

    The molecular distinction between acrodysostosis and Carney complex mutations at the protein level was unclear; biochemical comparison showed that acrodysostosis mutations impair cAMP binding in one domain without destabilizing the protein, whereas CNC mutations at homologous residues additionally accelerate protein degradation, establishing a unified model where cAMP insensitivity alone causes hormone resistance while combined insensitivity and instability causes tumorigenesis.

    Evidence CRE-luciferase, BRET dissociation assay, domain-specific cAMP analog sensitivity, pulse-chase protein stability assays

    PMID:26405036

    Open questions at the time
    • Whether intermediate-stability mutations produce intermediate clinical phenotypes
    • Structural dynamics underlying domain-specific cAMP insensitivity
  17. 2016 Medium

    Whether PRKAR1A loss contributes to non-endocrine epithelial cancers was unclear; studies in lung adenocarcinoma cells showed that PRKAR1A knockdown activates ERK/Snail signaling to suppress E-cadherin, promoting proliferation and migration—extending the tumor suppressor role beyond CNC-associated tissues. Separately, pancreas-specific Prkar1a KO produced neuroendocrine carcinomas with 100% penetrance.

    Evidence Stable knockdown/overexpression in lung adenocarcinoma cells with ERK/Snail/E-cadherin epistasis rescue; Pdx1-Cre conditional KO with PKA assays, histopathology, electron microscopy

    PMID:27803029 PMID:27995993

    Open questions at the time
    • Frequency and relevance of PRKAR1A alterations in sporadic lung and pancreatic cancers
    • Whether ERK/Snail axis is the dominant pathway in all epithelial contexts

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how PKA directly activates Rac1 and B-Raf; which AKAP scaffolds determine the compartment-specific consequences of RIα loss; whether the mTOR interaction on autophagosomes functionally modulates autophagy in PRKAR1A-mutant tumors; and what determines tissue tropism of Carney complex tumors despite ubiquitous RIα expression.
  • Direct PKA substrate linking to Rac1 and B-Raf activation unknown
  • AKAP-dependent spatial regulation of RIα not characterized in disease models
  • Functional significance of RIα-mTOR interaction for autophagy not established
  • Tissue-specific modifiers of PRKAR1A haploinsufficiency largely unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 4
Localization
GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005768 endosome 1 GO:0005886 plasma membrane 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1643685 Disease 12 R-HSA-162582 Signal Transduction 10 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
ACBD3MTORPRKACAPRKACBRAC1RARA
Complex memberships
PKA type I holoenzyme (RIα₂–Cα₂)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 PRKAR1A (encoding the RI-alpha regulatory subunit of PKA) was identified as the product of the tissue-specific extinguisher locus TSE1; TSE1/RI-alpha-mediated extinction involves repression of basal PKA activity, reduced phosphorylation of CREB at Ser-133, and a corresponding reduction of in vivo protein binding at the target cAMP response element (CRE), thereby repressing hepatocyte-specific gene transcription. Concordant expression mapping, high-resolution chromosomal mapping, transfection of RI-alpha cDNA to phenocopy TSE1 extinction, in vivo footprinting at CRE Cell High 1832337 1889088
1991 Stable transfection of wild-type or cAMP-binding mutant RI-alpha alleles into hepatoma recipients produced an extinction phenotype indistinguishable from TSE1, demonstrating that the cAMP-binding activity of RI-alpha is required for its gene-repression function. Subtractive cDNA hybridization cloning, high-resolution chromosome mapping, stable transfection of wild-type and cAMP-binding-mutant RI-alpha into hepatoma cells Cell High 1889088
2000 Inactivating germline PRKAR1A mutations (frameshifts, insertions, deletions leading to premature stop codons) cause CNC; mutant mRNAs containing premature stop codons are unstable due to nonsense-mediated mRNA decay (NMD), so the truncated PRKAR1A protein products are absent in patient cells, establishing PRKAR1A as a tumor suppressor gene acting through haploinsufficiency. Genomic sequencing of 54 CNC kindreds, linkage analysis, quantitative mRNA analysis demonstrating NMD, immunoblot confirming absence of truncated protein Human molecular genetics High 11115848
2002 An expressed PRKAR1A splicing mutation (intron 6 IVS+1G>T causing exon 6 skipping) produces a shorter but detectable RIα protein that activates PKA signaling at the nuclear level, demonstrating that altered PRKAR1A function (not just complete loss) is sufficient to augment PKA activity and promote tumorigenesis. Sequencing, RT-PCR detection of expressed mutant protein, in vitro functional studies of nuclear PKA-mediated phosphorylation, LOH analysis of tumors American journal of human genetics High 12424709
2003 In cells bearing PRKAR1A-inactivating mutations, PKA activity (basal and cAMP-stimulated) is augmented and the normal PKA-mediated inhibition of ERK1/2 (MAPK pathway) is lost; instead, PKA stimulation by forskolin or isoproterenol increases LPA-induced ERK1/2 phosphorylation, cell metabolism, and proliferation, suggesting that reversal of PKA-mediated MAPK inhibition contributes to tumorigenesis. PKA enzymatic assays, quantitative mRNA analysis, immunoblot of ERK1/2 phosphorylation, cell proliferation and metabolism assays in mutant vs. normal lymphoblasts and a pituitary tumor cell line Human molecular genetics High 12812976
2003 PRKAR1A was found to physically interact with the peripheral-type benzodiazepine receptor (PBR)-associated protein PAP7; both PAP7 and PRKAR1A are co-expressed and co-regulated in steroidogenic tissues, and PAP7 is decreased alongside PRKAR1A in CNC lymphocytes and PPNAD nodules, implicating a PRKAR1A-PAP7 complex in hormone-induced steroid biosynthesis. Molecular cloning, chromosomal mapping, immunohistochemistry in PPNAD and lymphoblast tissues, co-expression analysis FASEB journal Medium 12692076
2004 Prkar1a haploinsufficiency in mice predisposes to extracardiac tumorigenesis (sarcomas, hepatocellular carcinomas with myxomatous differentiation); tumors did not show Prkar1a LOH, indicating that haploinsufficiency alone predisposes to tumorigenesis but distinct secondary genetic events are required for frank tumor formation. Prkar1a(+/-) mouse model, tumor histopathology, LOH analysis Proceedings of the National Academy of Sciences of the United States of America High 15371594
2004 Antisense-mediated downregulation of Prkar1a in transgenic mice (tTA/X2AS line) leads to increased total type II PKA activity, higher RIIbeta protein levels, and development of thyroid and adrenocortical hyperplasia, lymphomas, and mesenchymal tumors—recapitulating Carney complex features and supporting RIalpha's tumor suppressor role. Tetracycline-responsive antisense transgene, enzymatic PKA assays, immunoblot for PKA subunits, histopathology, allelic loss analysis at Prkar1a locus Journal of medical genetics High 15591278
2006 In adrenocortical tissue from CNC patients bearing PRKAR1A mutations, there is increased cAMP-stimulated PKA activity, decreased RIα expression, and compensatory increases in other PKA subunits; these changes are accompanied by increased phosphorylated ERK1/2, B-Raf, p-MEK1/2, and p-c-Myc (but not p-Akt), identifying the B-Raf/MEK/ERK axis as a downstream effector of dysregulated PKA in PRKAR1A-mutant adrenocortical disease. PKA enzymatic assays, quantitative mRNA and immunoblot of PKA subunits, immunoassays and immunohistochemistry for ERK1/2, B-Raf, MEK1/2, c-Myc, Akt in patient adrenocortical samples The Journal of clinical endocrinology and metabolism High 16569736
2006 In lymphocytes with PRKAR1A-inactivating mutations, there is increased ERK1/2 and B-Raf phosphorylation, MEK1/2 and c-Myc activation, and c-Raf-1 inhibition, leading to increased cell cycle rates and decreased apoptosis—demonstrating that partial RIα inactivation is sufficient to increase proliferation and survival without requiring loss of the second allele. Immunoblot for phospho-ERK1/2, B-Raf, MEK1/2, c-Myc, c-Raf-1; cell cycle analysis; apoptosis assays in PRKAR1A-mutant vs. normal lymphocytes Cancer research High 17079485
2007 PRKAR1A (RIα) localizes on Rab7-positive late endosomes and LC3-positive autophagosomal membranes; RIα physically interacts with mTOR kinase and affects its phosphorylation and activity; mTOR co-localizes with RIα- and LC3-positive membranes, placing the RIα-mTOR complex at the level of autophagosome maturation. Live-cell fluorescence imaging of tagged RIα, co-immunoprecipitation of RIα and mTOR, phosphorylation assays, colocalization with autophagosomal markers (LC3, Rab7) Autophagy Medium 17204847
2007 PRKAR1A gene is fused to RARA in a variant acute promyelocytic leukemia (APL), creating a PRKAR1A-RARA fusion oncogene; two splice variants of the fusion transcript were identified by RT-PCR and confirmed by FISH. RT-PCR, sequencing, FISH with PRKAR1A and RARA probes Blood Medium 17712046
2007 Complete pituitary-specific knockout of Prkar1a (in Pit1 lineage cells) leads to pituitary tumor formation with markedly elevated serum GH, demonstrating that complete loss of Prkar1a is sufficient to cause pituitary adenomas in mice, mirroring the human CNC phenotype. Cre-lox tissue-specific knockout (GHRH receptor promoter-Cre × Prkar1a conditional null), tumor histopathology, hormone measurement, immunostaining Molecular endocrinology High 17975024
2007 PKA balance among isozymes is critical for cell cycle control: reintroduction of wild-type PRKAR1A into PRKAR1A-haploinsufficient cells decreases aneuploidy and G2/M fraction; E2F1 was identified as a mediator of PKA-associated cell cycle changes by siRNA knockdown. Transfection of PKA subunit constructs into immortalized PRKAR1A-mutant cells, flow cytometry for cell cycle and aneuploidy, siRNA knockdown of E2F1, cAMP measurement, immunoblot for cyclins and E2F factors The Journal of clinical endocrinology and metabolism Medium 18056771
2007 Mutation of Prkar1a in osteoblast precursor cells leads to increased PKA activity, impaired osteoblast differentiation, and bone tumor formation; tumor cells showed down-regulation of bone differentiation markers and up-regulation of Wnt signaling pathway members, and exhibited enhanced growth in response to PKA-stimulating agents. Prkar1a(+/-) mouse tumor isolation, primary culture, immunohistochemistry, PKA activity assay, gene expression profiling, xenograft tumor formation in immunocompromised mice Molecular endocrinology High 17932105
2008 The expressed exon-6-deletion PRKAR1A mutant (RIαΔ6) exhibits diffuse cytoplasmic localization without formation of discrete RIα aggregates, fails to bind the catalytic subunit (Cα) at baseline or after cAMP stimulation, leads to decreased nuclear Cα, and produces higher PKA activity without increasing type II PKA subunits—distinct from null mutations. Confocal microscopy of GFP-tagged RIα and Cerulean-tagged Cα, PKA activity assays, immunoblot of PKA subunits and phosphorylated targets in transfected cells Cancer research High 18451138
2008 In vitro functional studies of seven expressed PRKAR1A mutations (spanning all functional RIα domains) show that each leads to increased PKA activity attributable to decreased binding of cAMP and/or the catalytic subunit, confirming that altered RIα function—not only haploinsufficiency—elevates PKA activity and is associated with tumorigenesis. In vitro transfection of mutant constructs, PKA activity assays, cAMP-binding assays, catalytic subunit binding assays Human mutation High 18241045
2008 Cardiac-specific loss of Prkar1a causes embryonic death at E11.5-12.5 with elevated PKA activity, decreased cardiomyocyte proliferation, downregulation of key cardiac transcription factors (SRF, Gata4, Nkx2-5), and myxomatous degeneration in heart walls—directly linking excess PKA activity to suppression of cardiac transcription and myxomagenesis. Cre-lox cardiac-specific KO, PKA activity assays, immunohistochemistry for transcription factors and proliferation markers, histopathological analysis Circulation High 18316483
2008 Tissue-specific Prkar1a ablation in neural crest cells causes schwannomas with near-complete loss of both NF1 and NF2 (Merlin) proteins despite increased transcript levels, indicating posttranscriptional suppression of neurofibromatosis proteins; Rac1 but not Erk or Akt signaling is activated in these tumors. Conditional KO in neural crest (TEC3KO mice), tumor histopathology, immunoblot for NF1/NF2 proteins and transcripts, signaling pathway analysis (Erk, Akt, Ras, Rac1, RhoA) Neoplasia High 18953430
2008 Loss of Prkar1a in neural crest-derived cells causes mesenchymal-to-epithelial transition (MET): constitutive PKA signaling leads to posttranslational downregulation of vimentin (rescued by proteasomal inhibition) and upregulation of E-cadherin in both in vivo schwannomas and in vitro null fibroblasts; vimentin downregulation was also confirmed in human CNC adrenal nodules. Conditional KO (neural crest-specific), immunohistochemistry for vimentin and E-cadherin, in vitro MET assays in Prkar1a-null MEFs, proteasome inhibitor experiments, human tissue IHC Cancer research High 18413734
2009 The PRKAR1A-RARα APL fusion protein can transform bone marrow progenitor/stem cells; it binds retinoic acid response elements as homodimers and heterodimers with RXRα; the RIIa domain mediates homodimerization and interaction with wild-type RIα but is not required for transformation; leukemic transformation critically depends on RXRα interaction (elimination of RXRα interaction or RXRα knockdown reduced transformation). Murine bone-marrow retroviral transduction/transformation assay, gel-shift assays, RXRα shRNA, point mutagenesis of RXRα-interaction domain, RXRα agonist treatment Blood High 19965660
2010 Adrenal cortex-specific Prkar1a knockout (AdKO) mice develop pituitary-independent Cushing syndrome with increased PKA activity, autonomous steroidogenic gene expression, deregulated adreno-cortical cell differentiation, increased proliferation, and resistance to apoptosis; R1α loss also leads to improper maintenance of fetal adrenocortical cells with centrifugal expansion, providing in vivo evidence that R1α loss alone is sufficient to induce bilateral hyperplasia. Adrenal cortex-specific Cre-lox KO, PKA activity assays, hormone measurements, histopathology, immunohistochemistry for differentiation and proliferation markers, apoptosis assays PLoS genetics High 20548949
2010 Prkar1a haploinsufficiency in mice acts synergistically with Trp53 or Rb1 heterozygosity and chemical skin carcinogenesis to induce tumors; Wnt signaling (CCND1, CTNNB1, LEF1, WNT3) is the main pathway activated by abnormal cAMP signaling; siRNA knockdown of Ctnnb1, E2f1, or Cdk4 inhibits proliferation of PRKAR1A-mutant human adrenal cells and arrests them at G0/G1. Double heterozygous mouse models (Prkar1a(+/-)/Trp53(+/-) and Prkar1a(+/-)/Rb1(+/-)), two-step skin carcinogenesis protocol, whole-genome transcriptome profiling, qRT-PCR array, immunohistochemistry, siRNA knockdown with cell cycle analysis Human molecular genetics High 20080939
2011 Simultaneous siRNA inactivation of PRKAR1A and PDE11A leads to an increase in cAMP-regulatory element-mediated transcriptional activity under basal conditions and after forskolin stimulation, establishing that PDE11A acts as a genetic modifier of the PRKAR1A/cAMP pathway relevant to adrenal and testicular tumorigenesis. siRNA co-knockdown of PRKAR1A and PDE11A in cells, CRE-luciferase reporter assay with and without forskolin, population genetics in 150 CNC patients The Journal of clinical endocrinology and metabolism Medium 21047926
2011 Recurrent gain-of-function PRKAR1A mutations (e.g., R368X, located in the cAMP-binding domain) impair the PKA response to cAMP stimulation, causing hormone resistance and acrodysostosis—a phenotype mechanistically distinct from the Carney complex mutations that cause haploinsufficiency. Germline mutation sequencing in three patients, clinical hormone resistance testing, in vitro PKA stimulation assays The New England journal of medicine High 21651393
2011 Novel PRKAR1A frameshift mutations in the last coding exon that escape NMD produce elongated proteins that are degraded by the proteasome (not the NMD pathway); proteasome inhibitors restore detection of the aberrant proteins, demonstrating that proteasomal surveillance is an additional mechanism producing PRKAR1A haploinsufficiency. Site-directed mutagenesis, in vitro transcription/translation, transfection in NCI-295/N-TERA/HEK293 cells, Western blot with and without proteasome inhibitors, RNA analysis in patient cells The Journal of clinical endocrinology and metabolism High 22205709
2011 Differential roles of PKA catalytic subunit isoforms: heterozygosity for Prkaca (Cα) rescues embryonic lethality of cardiac Prkar1a KO and suppresses schwannoma formation by >80% in neural crest KO mice; heterozygosity for Prkacb (Cβ) has minimal effect on cardiac phenotype but suppresses schwannoma formation by >80%, establishing that the developmental and tumor phenotypes of Prkar1a loss are mediated primarily by excess PKA-Cα activity. Genetic epistasis: introduction of Prkaca or Prkacb null alleles into Prkar1a-CKO and TEC3KO mice, PKA activity assays, tumor incidence monitoring, survival analysis Molecular endocrinology High 21852354
2012 The novel PRKAR1A p.T239A mutation (in cAMP-binding domain A) causes acrodysostosis by impairing cAMP-mediated GPCR signaling; mutant cells show markedly reduced CREB phosphorylation after forskolin stimulation, and CRE-luciferase reporter assays in HEK293 cells expressing the mutant confirm significantly impaired PKA response to cAMP. Sequencing, Western blot of phospho-CREB in patient lymphoblastoid cells, CRE-luciferase reporter assay in HEK293 cells transfected with mutant PRKAR1A The Journal of clinical endocrinology and metabolism Medium 22723333
2012 Rac1 activation downstream of PKA (due to Prkar1a KO) is required for suppression of Nf2/Merlin protein in schwannoma cells; loss of Rac1 in Prkar1a/Rac1 double KO Schwann cells re-expresses Nf2 protein and suppresses tumor formation; activated Rac1 downregulates Nf2 in vitro in a Pak-dependent manner, establishing a bidirectional signaling relationship between Rac1 and Nf2 modulated by PKA. Double conditional KO of Prkar1a and Rac1 in Schwann cells, tumor incidence analysis, immunoblot for Nf2/Merlin, in vitro activated-Rac1 overexpression with Pak inhibition Oncogene High 23045281
2013 RIα knockdown (PRKAR1A inactivation) in HEK293 cells increases basal and stimulated total cytoplasmic and mitochondrial PKA activity but decreases plasma membrane PKA response and increases basal membrane PKA activity; RIα inactivation also raises cAMP levels in cytoplasm, at the outer mitochondrial membrane, and at the plasma membrane—demonstrating compartment-specific, spatially distinct dysregulation of the cAMP/PKA pathway. FRET-based reporters (AKAR3 global, compartment-targeted AKAR3 variants, Epac1-camps for cAMP) in live cells; siRNA knockdown of RIα; Western blot of phospho-VASP; validated in human adrenal cells with RIα-inactivating mutation Human molecular genetics High 24122441
2013 Loss of Prkar1a in Schwann cells (SCKO) causes a persistent axonal sorting defect and unexpectedly decreases Schwann cell proliferation in vivo; in the rare sorted Schwann cells, myelination is premature and correlated with global increase in the cAMP-regulated transcription factor Oct-6 and myelin basic protein expression, revealing PKA as a required regulator of axon sorting and a negative regulator of Schwann cell proliferation in vivo. SC-specific conditional Prkar1a KO (Prkar1a-SCKO mice), PKA activity assays, histological and electron microscopic analysis of nerve, immunohistochemistry for Oct-6 and MBP, in vitro SC cultures The Journal of neuroscience High 24227708
2015 Functional characterization of acrodysostosis PRKAR1A mutations shows that impaired cAMP binding is the common molecular mechanism preventing PKA activation, affecting only the domain containing the mutation. In contrast, Carney complex mutations at homologous residues show additional accelerated PRKAR1A protein degradation—demonstrating that a cAMP binding defect alone causes acrodysostosis, whereas multiple defects including protein instability cause CNC. CRE-luciferase reporter assay, BRET assay for cAMP-induced RIα dissociation from catalytic subunit, cAMP analog sensitivity (domain A vs. domain B specific analogs), modeling studies, pulse-chase protein stability assays The Journal of biological chemistry High 26405036
2016 In lung adenocarcinoma cells, PRKAR1A loss activates ERK/Snail signaling, which in turn suppresses E-cadherin expression, promoting cell proliferation and migration; re-expression of PRKAR1A suppresses these effects, and elevated E-cadherin rescues the PRKAR1A-KD phenotype, placing PRKAR1A upstream of the ERK-Snail-E-cadherin axis. Stable PRKAR1A knockdown and overexpression in lung adenocarcinoma cell lines, in vitro proliferation and migration assays, in vivo colonization assay in nude mice, Western blot of ERK/Snail/E-cadherin pathway Scientific reports Medium 27995993
2016 Pdx1-specific Prkar1a KO in the mouse pancreas leads to endocrine or mixed endocrine/acinar pancreatic carcinomas with 100% penetrance by 4-5 months, with high PKA activity confirmed biochemically and primary neuroendocrine tumor nature confirmed by electron microscopy, establishing PRKAR1A as a tumor suppressor in the pancreas through a PKA-dependent mechanism. Conditional Prkar1a KO (pdx1-Cre), PKA activity assays, histopathology, immunohistochemistry, electron microscopy (secretory granules), metastasis documentation Endocrine-related cancer High 27803029
2019 Glioma-derived exosomal miR-92a targets PRKAR1A mRNA in myeloid-derived suppressor cells (MDSCs), activating MDSC proliferation and function; this establishes PRKAR1A as a direct target of miR-92a in the immunosuppressive tumor microenvironment. miRNA sequencing of exosomes, luciferase reporter assay for miR-92a targeting of PRKAR1A 3'UTR, in vitro MDSC differentiation assays with exosome treatment, in vivo MDSC induction International journal of cancer Medium 30536597
2008 A large PRKAR1A in-frame deletion of exon 3 (predicted to lack the primary site for catalytic subunit interaction) results in impaired cAMP binding and PKA activation in vitro; this expressed mutant protein appears more harmful than allelic loss, and the carrier had a more severe CNC phenotype. Southern hybridization to detect large deletion, in vitro transfection of mutant PRKAR1A, cAMP-binding assay, PKA activity assay Clinical cancer research Medium 18223213

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Human molecular genetics 316 11115848
2009 Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. The Journal of clinical endocrinology and metabolism 300 19293268
2003 Molecular and functional analysis of PRKAR1A and its locus (17q22-24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity. Cancer research 204 14500362
1991 The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase. Cell 185 1832337
2004 Minireview: PRKAR1A: normal and abnormal functions. Endocrinology 165 15331577
2010 The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. Clinical genetics 150 20507346
2002 Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD. American journal of human genetics 148 12424709
1990 A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1. Cell 147 1971524
2010 Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Human mutation 146 20358582
2019 Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/Hbp1 and microRNA-92a/Prkar1a pathways. International journal of cancer 139 30536597
2002 Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease. The Journal of clinical endocrinology and metabolism 139 12213893
1991 Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A. Cell 138 1889088
2011 Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance. The New England journal of medicine 121 21651393
2006 Impaired nociception and inflammatory pain sensation in mice lacking the prokineticin receptor PKR1: focus on interaction between PKR1 and the capsaicin receptor TRPV1 in pain behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 120 16793879
2004 Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice. Proceedings of the National Academy of Sciences of the United States of America 120 15371594
2007 The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood 94 17712046
2004 A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. Journal of medical genetics 93 15591278
2010 Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice. PLoS genetics 91 20548949
2006 A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. The Journal of clinical endocrinology and metabolism 88 16464939
2012 PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct syndromes with or without GPCR-signaling hormone resistance. The Journal of clinical endocrinology and metabolism 83 23043190
2010 Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype. The Journal of clinical endocrinology and metabolism 81 21047926
2017 Genomic Analysis of Pigmented Epithelioid Melanocytomas Reveals Recurrent Alterations in PRKAR1A, and PRKCA Genes. The American journal of surgical pathology 78 28796000
2002 Regulatory subunit type I-alpha of protein kinase A (PRKAR1A): a tumor-suppressor gene for sporadic thyroid cancer. Genes, chromosomes & cancer 77 12203783
2008 Large deletions of the PRKAR1A gene in Carney complex. Clinical cancer research : an official journal of the American Association for Cancer Research 76 18223213
2003 Protein kinase-A activity in PRKAR1A-mutant cells, and regulation of mitogen-activated protein kinases ERK1/2. Human molecular genetics 76 12812976
2014 PRKAR1A in the development of cardiac myxoma: a study of 110 cases including isolated and syndromic tumors. The American journal of surgical pathology 75 24618615
2003 Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease! FEBS letters 67 12829237
2002 Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit (PRKAR1A) in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas" (Carney complex). Annals of the New York Academy of Sciences 66 12119264
2002 Sequence analysis of the PRKAR1A gene in sporadic somatotroph and other pituitary tumours. Clinical endocrinology 64 12354125
2008 In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Human mutation 58 18241045
2006 PRKAR1A Mutations and protein kinase A interactions with other signaling pathways in the adrenal cortex. The Journal of clinical endocrinology and metabolism 58 16569736
2008 Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors. Cancer research 56 18451138
2007 Pituitary-specific knockout of the Carney complex gene Prkar1a leads to pituitary tumorigenesis. Molecular endocrinology (Baltimore, Md.) 55 17975024
2008 Heart-specific ablation of Prkar1a causes failure of heart development and myxomagenesis. Circulation 53 18316483
2010 Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/- or Rb1+/- backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling. Human molecular genetics 52 20080939
2010 PRKAR1A is overexpressed and represents a possible therapeutic target in human cholangiocarcinoma. International journal of cancer 52 20824711
2018 Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the classic DNAJB1-PRKACA fusion. Hepatology (Baltimore, Md.) 51 29222914
2011 A large family with Carney complex caused by the S147G PRKAR1A mutation shows a unique spectrum of disease including adrenocortical cancer. The Journal of clinical endocrinology and metabolism 51 22112814
2012 Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations. The Journal of clinical endocrinology and metabolism 49 22259056
2008 Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain. European journal of endocrinology 46 18694911
1989 Hormonal regulation of TSE1-repressed genes: evidence for multiple genetic controls in extinction. Molecular and cellular biology 45 2571076
2015 Consistent copy number changes and recurrent PRKAR1A mutations distinguish Melanotic Schwannomas from Melanomas: SNP-array and next generation sequencing analysis. Genes, chromosomes & cancer 44 26031761
2013 Deletions of the PRKAR1A locus at 17q24.2-q24.3 in Carney complex: genotype-phenotype correlations and implications for genetic testing. The Journal of clinical endocrinology and metabolism 44 24170103
2007 Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1) and PKR2 throughout mouse gestation. Placenta 42 17531315
2021 MANAGEMENT OF ENDOCRINE DISEASE: Carney complex: clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene. European journal of endocrinology 41 33444222
2014 PC1, a non-peptide PKR1-preferring antagonist, reduces pain behavior and spinal neuronal sensitization in neuropathic mice. Pharmacological research 41 25434589
2012 Structural insights into the Pseudomonas aeruginosa type VI virulence effector Tse1 bacteriolysis and self-protection mechanisms. The Journal of biological chemistry 41 22700987
2012 Structural insights into the effector-immunity system Tse1/Tsi1 from Pseudomonas aeruginosa. PloS one 41 22792331
2016 Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 39 26763073
2003 GH-secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23-24. Clinical endocrinology 38 12641630
2012 Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer. Endocrine-related cancer 36 22514108
2006 PRKAR1A mutations in primary pigmented nodular adrenocortical disease. Pituitary 36 17036196
2020 Genomic and Clinicopathologic Characteristics of PRKAR1A-inactivated Melanomas: Toward Genetic Distinctions of Animal-type Melanoma/Pigment Synthesizing Melanoma. The American journal of surgical pathology 33 32118628
2009 Large cell calcifying Sertoli cell tumor: a clinicopathologic study of 1 malignant and 3 benign tumors using histomorphology, immunohistochemistry, ultrastructure, comparative genomic hybridization, and polymerase chain reaction analysis of the PRKAR1A gene. Human pathology 33 20004940
2007 An immortalized human cell line bearing a PRKAR1A-inactivating mutation: effects of overexpression of the wild-type Allele and other protein kinase A subunits. The Journal of clinical endocrinology and metabolism 33 18056771
2012 PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance. The Journal of clinical endocrinology and metabolism 32 22723333
2006 PRKAR1A inactivation leads to increased proliferation and decreased apoptosis in human B lymphocytes. Cancer research 32 17079485
2015 Functional Characterization of PRKAR1A Mutations Reveals a Unique Molecular Mechanism Causing Acrodysostosis but Multiple Mechanisms Causing Carney Complex. The Journal of biological chemistry 31 26405036
2008 Targeted deletion of Prkar1a reveals a role for protein kinase A in mesenchymal-to-epithelial transition. Cancer research 31 18413734
2007 mTOR kinase and the regulatory subunit of protein kinase A (PRKAR1A) spatially and functionally interact during autophagosome maturation. Autophagy 30 17204847
2014 Follicular thyroid cancers demonstrate dual activation of PKA and mTOR as modeled by thyroid-specific deletion of Prkar1a and Pten in mice. The Journal of clinical endocrinology and metabolism 29 24512487
2007 Mutation of Prkar1a causes osteoblast neoplasia driven by dysregulation of protein kinase A. Molecular endocrinology (Baltimore, Md.) 29 17932105
2005 PRKAR1A gene mutation in patients with cardiac myxoma. International journal of cardiology 29 15982496
2003 Molecular cloning, chromosomal localization of human peripheral-type benzodiazepine receptor and PKA regulatory subunit type 1A (PRKAR1A)-associated protein PAP7, and studies in PRKAR1A mutant cells and tissues. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 12692076
2008 Tissue-specific ablation of Prkar1a causes schwannomas by suppressing neurofibromatosis protein production. Neoplasia (New York, N.Y.) 28 18953430
2006 PKR1 encodes an assembly factor for the yeast V-type ATPase. The Journal of biological chemistry 28 16926153
2020 Ovarian cancer derived PKR1 positive exosomes promote angiogenesis by promoting migration and tube formation in vitro. Cell biochemistry and function 27 32876972
2017 PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex. European journal of endocrinology 27 28522647
2013 Novel mutations of the PRKAR1A gene in patients with acrodysostosis. Clinical genetics 27 23425300
2005 Molecular and immunohistochemical investigation of protein kinase a regulatory subunit type 1A (PRKAR1A) in odontogenic myxomas. Genes, chromosomes & cancer 27 16001434
2012 Crystal structure of type VI effector Tse1 from Pseudomonas aeruginosa. FEBS letters 25 22750141
2010 PRKAR1A and the evolution of pituitary tumors. Molecular and cellular endocrinology 25 20451576
2016 PRKAR1A is a functional tumor suppressor inhibiting ERK/Snail/E-cadherin pathway in lung adenocarcinoma. Scientific reports 24 27995993
1985 The role of polypeptides L and NS in the transcription process of vesicular stomatitis virus New Jersey using the temperature-sensitive mutant tsE1. The Journal of general virology 24 2987393
2018 Expanding the phenotypic spectrum of variants in PDE4D/PRKAR1A: from acrodysostosis to acroscyphodysplasia. European journal of human genetics : EJHG 23 30006632
2011 Differential role of PKA catalytic subunits in mediating phenotypes caused by knockout of the Carney complex gene Prkar1a. Molecular endocrinology (Baltimore, Md.) 23 21852354
2011 Prokineticin receptor 1 (PKR1) signalling in cardiovascular and kidney functions. Cardiovascular research 23 21856786
2009 Association of the M1V PRKAR1A mutation with primary pigmented nodular adrenocortical disease in two large families. The Journal of clinical endocrinology and metabolism 23 19915019
2016 Prkar1a gene knockout in the pancreas leads to neuroendocrine tumorigenesis. Endocrine-related cancer 22 27803029
2022 PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction. Frontiers in immunology 21 35592331
2018 PK2β ligand, a splice variant of prokineticin 2, is able to modulate and drive signaling through PKR1 receptor. Neuropeptides 21 30253862
2012 Structural insight into how Pseudomonas aeruginosa peptidoglycanhydrolase Tse1 and its immunity protein Tsi1 function. The Biochemical journal 21 22931054
2009 Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}. Blood 21 19965660
2008 A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations. Clinical endocrinology 21 18445140
2004 Eyelid myxoma in Carney complex without PRKAR1A allelic loss. American journal of medical genetics. Part A 21 15368482
2000 PECAM1, MPO and PRKAR1A at chromosome 17q21-q24 and susceptibility for multiple sclerosis in Sweden and Sardinia. Journal of neuroimmunology 21 10900349
2019 Somatic PRKAR1A Gene Mutation in a Nonsyndromic Metastatic Large Cell Calcifying Sertoli Cell Tumor. Journal of the Endocrine Society 19 31286102
2012 Rac1 is required for Prkar1a-mediated Nf2 suppression in Schwann cell tumors. Oncogene 19 23045281
2011 In vitro studies of novel PRKAR1A mutants that extend the predicted RIα protein sequence into the 3'-untranslated open reading frame: proteasomal degradation leads to RIα haploinsufficiency and Carney complex. The Journal of clinical endocrinology and metabolism 19 22205709
2010 Neural crest-specific loss of Prkar1a causes perinatal lethality resulting from defects in intramembranous ossification. Molecular endocrinology (Baltimore, Md.) 19 20534695
2022 Sporadic superficial angiomyxomas demonstrate loss of PRKAR1A expression. Histopathology 18 34532875
2022 Large cell calcifying Sertoli cell tumour: a contemporary multi-institutional case series highlighting the diagnostic utility of PRKAR1A immunohistochemistry. Histopathology 18 34780072
2014 Comparison of the effects of PRKAR1A and PRKAR2B depletion on signaling pathways, cell growth, and cell cycle control of adrenocortical cells. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 25268545
2009 The Carney complex gene PRKAR1A plays an essential role in cardiac development and myxomagenesis. Trends in cardiovascular medicine 18 19577711
2022 Attempting to Solve the Pigmented Epithelioid Melanocytoma (PEM) Conundrum: PRKAR1A Inactivation Can Occur in Different Genetic Backgrounds (Common, Blue, and Spitz Subgroups) With Variation in Their Clinicopathologic Characteristics. The American journal of surgical pathology 17 35319526
2021 Role of CNC1 gene in TDP-43 aggregation-induced oxidative stress-mediated cell death in S. cerevisiae model of ALS. Biochimica et biophysica acta. Molecular cell research 16 33647321
2021 PRKAR1A and Thyroid Tumors. Cancers 16 34359735
2013 Inactivation of the Carney complex gene 1 (PRKAR1A) alters spatiotemporal regulation of cAMP and cAMP-dependent protein kinase: a study using genetically encoded FRET-based reporters. Human molecular genetics 16 24122441
2013 The protein kinase A regulatory subunit R1A (Prkar1a) plays critical roles in peripheral nerve development. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 24227708
2020 Methane Ameliorates Lipopolysaccharide-Induced Acute Orchitis by Anti-inflammatory, Antioxidative, and Antiapoptotic Effects via Regulation of the PK2/PKR1 Pathway. Oxidative medicine and cellular longevity 15 32922653