ArticleJCI insight2018
Activating PRKACB somatic mutation in cortisol-producing adenomas.
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.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- The germline landscape of pituitary adenomas: established and emerging predisposition genes.The Journal of clinical endocrinology and metabolism · 2026Review
- The βBritish journal of pharmacology · 2026Article
- Functional divergence of protein kinase A regulatory subunit Iβ variants: the importance of N3A motifs in PKA regulation.The FEBS journal · 2026Article
- Review
- Molecular characterization of archival adrenal tumor tissue from patients with ACTH-independent Cushing syndrome.The Journal of steroid biochemistry and molecular biology · 2025Review
- Alpha-estradiol and (R)-(-)-ibuprofen inhibit gastric cancer progression via GLI1 G-quadruplex.Frontiers in pharmacology · 2025Article
- The molecular genetics of adrenal cushing.Hormones (Athens, Greece) · 2024Review
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Molecular and Genetics Perspectives on Primary Adrenocortical Hyperfunction Disorders.International journal of molecular sciences · 2024Review
- PRKACB is a novel imprinted gene in marsupials.Epigenetics & chromatin · 2024Article
- Molecular determinants and signaling effects of PKA RIα phase separation.Molecular cell · 2024Article
- Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.Science advances · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Classification of Cushing's syndrome PKAc mutants based upon their ability to bind PKI.The Biochemical journal · 2023Article
- USP13 genetics and expression in a family with thyroid cancer.Endocrine · 2022Article
- Mislocalization of protein kinase A drives pathology in Cushing's syndrome.Cell reports · 2022Article
- Genetic Alterations in Benign Adrenal Tumors.Biomedicines · 2022Review
- The Tails of Protein Kinase A.Molecular pharmacology · 2022Review
- Overview of the 2022 WHO Classification of Adrenal Cortical Tumors.Endocrine pathology · 2022Review
- Targeted Mutational Analysis of Cortisol-Producing Adenomas.The Journal of clinical endocrinology and metabolism · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
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.
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