Fig. 7.

Disease mutations associated with the PKA C-subunits. Cushing disease mutations (red dots) are associated mostly with the Cα-subunit. They cluster around the activation segment and interfere with regulation by the R-subunits. A newly discovered Cushing disease mutation (teal dot) is located in the Nt-helix and shows correlated changes in the activation segment (Walker et al., 2021). Mutations that correlate with Sonic Hedgehog signaling (yellow dots) have been identified in Cβ and cluster around the active site cleft and the docking surface for the PKI helix (Palencia-Campos et al., 2020). The N-lobe of the kinase core is in white; the C-lobe is in tan. The A-helix and the activation segment are highlighted in teal, and the PKI peptide is red. ATP and the two Mg⁺⁺ ions are black.