Figure 7.

Model of evolution of PKA C subunits. The catalytic core is a conserved feature of the eukaryotic-like kinases (ELKs). The ePKs differ from ELKs through the attainment of the activation loop, typically involving a phosphorylatable Thr which can regulate the catalytic core into active/inactive conformations, and the G, H, and I helices (“GHI domain”), serving as docking motifs for substrates (197). The C-tail is a conserved feature of the AGC group of ePKs, and is highly regulated and essential for catalytic activity (171). The N-tail of PKA Cα and Cβ includes the A helix, which interacts with AKIP in Cα1 residues 15–29 (128). This segment is shared among all C subunit isoforms, whereas the alternative N-termini are located N-terminal to the AKIP-docking site. These alterations give rise to possible functional effects in different C subunit isoforms (“myristic acid,” “inducible helix,” “…”). Figure inspired by Taylor et al. (171, 197). PDB, 3FJQ.