Genetic Approaches to Studying Protein Kinase C

Abstract

The mammalian protein kinase C (PKC) super family is comprised of 10 gene products, and this large number of isozymes has presented a challenge to understanding the function of individual family members. Nonselective pharmacological approaches have implicated PKCs in a number of physiological processes and have identified numerous PKC substrates. However, it has been difficult to assign individual functions and substrates to specific isozymes. This is partly because few cell-permeable molecules are available for use as isozyme-selective PKC inhibitors. In addition, PKC isozymes exhibit broadly overlapping substrate specificities in vitro. This has led many investigators to suggest that there is redundancy of function within the PKC family. On the other hand, several studies have identified second messengers that activate subgroups of PKC isozymes, whereas others have identified isozyme-specific patterns of subcellular localization before and after PKC activation. These findings suggest that there is functional specificity among different members of the PKC family.