Localization, anchoring, and functions of protein kinase C isozymes in the heart

Although protein kinase C (PKC) was identified more than 20 years ago, and is involved in a wide variety of essential cellular processes, assigning specific roles to each PKC isozyme has proved difficult. Results over the last few years have suggested that much of the specificity of activated PKC isozymes is attributed to their subcellular localization bringing them into close proximity to a subset of substrates. Our laboratory has taken advantage of the importance of PKC localization and studied the way in which PKC isozymes are anchored. We have identified PKC anchoring proteins (RACKs or Receptors for Activated C Kinase) and used information about interaction sites between PKC isozymes and their respective RACKs to design peptides which modulate translocation of specific PKC isozymes to the functional site. These isozyme-specific peptides can be delivered into isolated or cultured cells or expressed in transgenic mice to determine the role of specific PKC isozymes in particular functions. Here we will describe the isozymes-specific peptide activators and inhibitors that we have developed and the specific functions of each isozyme in cardiac ventricular tissue.