Evidence map›Paper›PMID 29669941›Full record

ArticleJCI insight2018

Activating PRKACB somatic mutation in cortisol-producing adenomas.

Stéphanie Espiard, Matthias J Knape, Kerstin Bathon, Guillaume Assié, Marthe Rizk-Rabin, Simon Faillot, Windy Luscap-Rondof, Daniel Abid, Laurence Guignat, Davide Calebiro and 3 more

Open access · goldAbstract readCase ReportsComparative Study
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
  2. The βBritish journal of pharmacology · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. The molecular genetics of adrenal cushing.Hormones (Athens, Greece) · 2024
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. The Tails of Protein Kinase A.Molecular pharmacology · 2022
    Review
  19. Review
  20. Targeted Mutational Analysis of Cortisol-Producing Adenomas.The Journal of clinical endocrinology and metabolism · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 4 countries.

Stéphanie EspiardCochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France.
Matthias J KnapeUniversity of Kassel, Department of Biochemistry, Kassel, Germany.
Kerstin BathonInstitute of Pharmacology and Toxicology and Bio-Imaging Center/Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Guillaume AssiéCochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France.
Marthe Rizk-RabinCochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France.
Simon FaillotCochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France.
Windy Luscap-RondofCochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France.
Daniel AbidUniversity of Kassel, Department of Biochemistry, Kassel, Germany.
Laurence GuignatCenter for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
Davide CalebiroInstitute of Pharmacology and Toxicology and Bio-Imaging Center/Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
Friedrich W HerbergUniversity of Kassel, Department of Biochemistry, Kassel, Germany.
Constantine A StratakisSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
Jérôme BertheratCochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France.
Délégation Paris 5 · FRUniversity of Kassel · DEUniversity of Würzburg · DEEunice Kennedy Shriver National Institute of Child Health and Human Development · USHôpital Cochin · FR

Funding

Molecular Genetics of Endocrine Tumors and Related DisordersZIAHD008920 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI STRATAKIS, CONSTANTINE A. · 2012 to 2021
$25.8M
6 · The paper itself

Abstract

Mutations in the gene encoding the protein kinase A (PKA) catalytic subunit α have been found to be responsible for cortisol-producing adenomas (CPAs). In this study, we identified by whole-exome sequencing the somatic mutation p.S54L in the PRKACB gene, encoding the catalytic subunit β (Cβ) of PKA, in a CPA from a patient with severe Cushing syndrome. Bioluminescence resonance energy transfer and surface plasmon resonance assays revealed that the mutation hampers formation of type I holoenzymes and that these holoenzymes were highly sensitive to cAMP. PKA activity, measured both in cell lysates and with recombinant proteins, based on phosphorylation of a synthetic substrate, was higher under basal conditions for the mutant enzyme compared with the WT, while maximal activity was lower. These data suggest that at baseline the PRKACB p.S54L mutant drove the adenoma cells to higher cAMP signaling activity, probably contributing to their autonomous growth. Although the role of PRKACB in tumorigenesis has been suggested, we demonstrated for the first time to our knowledge that a PRKACB mutation can lead to an adrenal tumor. Moreover, this observation describes another mechanism of PKA pathway activation in CPAs and highlights the particular role of residue Ser54 for the function of PKA.

Indexed as

AdenomaAdrenalectomyAdrenal Gland NeoplasmsAdrenal InsufficiencyAdultCatalytic DomainCushing SyndromeCyclic AMP-Dependent Protein Kinase Catalytic SubunitsCyclic AMP-Dependent Protein KinasesCyclic AMP Receptor ProteinExome SequencingFemaleHoloenzymesHumansHydrocortisoneMutationCyclic AMP-Dependent Protein Kinase Catalytic SubunitsCyclic AMP-Dependent Protein KinasesCyclic AMP Receptor ProteinHoloenzymesHydrocortisonePRKACB protein, humanEndocrinologyGeneticsMolecular geneticsProtein kinases

Identifiers

PMID29669941
PMCPMC5931119
OpenAlexW2801631623

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.