Activation of protein kinase C (PKC) isoforms is a multistep depending on localization, post translational modifications and intramolecular interactions. PKCs contain a modular regulatory domain (bottom left, blue, orange, brown) and a typical kinase domain (green). Membrane association allows priming phosphorylations in the kinase domain (top right), promoting full activity. Additional regulation of activity occurs through autoinhibitory binding of the pseudosubstrate domain in the substrate binding pocket of the primed kinase (bottom right). Image kindly supplied by Jeroen Claus and Peter Parker.