Mitchell H Omar, Dominic P Byrne, Safal Shrestha, Tyler M Lakey, Kyung-Soon Lee, Sophia M Lauer, Kerrie B Collins, Leonard A Daly, Claire E Eyers, Geoffrey S Baird, Shao-En Ong, Natarajan Kannan, Patrick A Eyers, John D Scott
Adrenal Cushing's syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a Cushing's driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAcW196G is unexpectedly distinct from other described Cushing's variants, exhibiting retained association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs)...
February 23, 2024: Science Advances