{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:02:48Z","timestamp":1790056968298,"version":"4.0.1"},"reference-count":36,"publisher":"American Society for Clinical Investigation","issue":"8","funder":[{"name":"PROMEX foundation","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"BMBF","award":["0316177 F"],"award-info":[{"award-number":["0316177 F"]}]},{"name":"intramural research program of the NICHD","award":["Z01 HD008920"],"award-info":[{"award-number":["Z01 HD008920"]}]},{"name":"DFG","award":["He 1818\/10"],"award-info":[{"award-number":["He 1818\/10"]}]},{"DOI":"10.13039\/501100009379","name":"IZKF W\u00fcrzburg","doi-asserted-by":"crossref","award":["grant B281"],"award-info":[{"award-number":["grant B281"]}],"id":[{"id":"10.13039\/501100009379","id-type":"DOI","asserted-by":"crossref"}]},{"name":"E-RARE program","award":["ANR-13-RARE-008"],"award-info":[{"award-number":["ANR-13-RARE-008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,19]]},"abstract":"<jats:p>\n                    Mutations in the gene encoding the protein kinase A (PKA) catalytic subunit \u03b1 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\n                    <jats:italic>PRKACB<\/jats:italic>\n                    gene, encoding the catalytic subunit \u03b2 (C\u03b2) 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\n                    <jats:italic>PRKACB<\/jats:italic>\n                    in tumorigenesis has been suggested, we demonstrated for the first time to our knowledge that a\n                    <jats:italic>PRKACB<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.98296","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T11:02:49Z","timestamp":1524049369000},"source":"Crossref","is-referenced-by-count":60,"title":["Activating PRKACB somatic mutation in cortisol-producing adenomas"],"prefix":"10.1172","volume":"3","author":[{"given":"St\u00e9phanie","family":"Espiard","sequence":"first","affiliation":[{"name":"Cochin Institute, Paris Descartes University, CNRS (UMR 8104)\/Inserm (U1016), Paris, France."},{"name":"Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias 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