Inhibition of protein kinase C--do we, can we, and should we?

The second messenger responsive protein kinase C (PKC) family has promised much as therapeutic targets. Indeed, there has been excellent progress in the development of highly selective inhibitors for this class of kinases. The key to the further development and use of inhibitors selective within the family depends upon our understanding of the involvement of PKC in human disease. Recent work in model systems ex vivo has modified the simplistic view of PKC control and broadened the spectrum of signalling pathway involvement. The consequence is that there is a need to reassess the role of PKC that to date has coloured our view of PKC and disease. These developments, their implications, and the future assessment of PKC as a target are discussed.