Recurrent Acrodysostosis-Related PKA RIα Mutant Reveals a Novel Mechanism of Aberrant PKA Deactivation.

ABSTRACT: Protein kinase A (PKA) is essential in converting extracellular signals into tightly regulated cellular responses controlling vital processes such as growth, development, and gene expression. Activation of PKA is controlled by the binding of cAMP to the regulatory subunit of PKA (R). Several mutations in the ubiquitous RIα isoform of R cause Acrodysostosis 1 (ACRO), a disease characterized by resistance to thyroid-stimulating and parathyroid hormones leading to severe congenital malformations. This work examines the recurrent R366X truncation ACRO mutant, which exhibits severe PKA hypoactivation due to loss of sensitivity to cAMP and the impairment of allosteric networks. The R366X RIα mutant has been previously studied via X-ray crystallography, but the crystal structure only captured the

SUBMITTER: Della Libera L 

PROVIDER: S-EPMC12851291 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature