Camp-dependent protein kinase: Structural basis for activation and subcellular localization

cAMP-dependent protein kinase (cAPK) is one of the simplest members of the protein kinase family and has served in many ways as a prototype for all eukaryotic protein kinases. The structure of the catalytic (C) subunit coupled with a detailed dissecting of the kinetics of the phosphoryl transfer reaction has defined a dynamic set of steps that correlate opening and closing of the active site cleft with phosphoryl transfer and product release. The structure and mutational analysis of the inhibitors of the C-subunit, both the regulatory subunits and the heat stable protein kinase inhibitors, have revealed diversity in how the C-subunit uses different surfaces to achieve high affinity binding of its different classes of inhibitors. The modular and multifunctional nature of these inhibitors are defining a broad scope for the role that they play in the trafficking and subcellular localization of cAPK.