Critical targets of protein kinase C in differentiation of tumour cells

The ultimate target of pharmacological research is to find new drugs for tr eating human diseases such as cancer. Agents causing differentiation and th us growth arrest should be particularly useful in this regard. A potential target for such anticancer therapy is the enzyme family protein kinase C (P KC), which is involved in the transduction of signals for cell proliferatio n, differentiation and apoptosis. Our recent work showing the induction of differentiation in melanoma cells by an activator of one PKC isoform, PKC d elta, touches on several important areas of investigation, which will form the basis of this review: the role of individual isoforms of PKC, their dow nstream targets and their specific substrates, the mechanism of activation of specific Penes involved in the differentiation process, and the molecula r basis for the morphological changes associated with differentiation. The central role that PKC plays in these processes points to the need for a gre ater understanding of the signalling pathways utilized by individual isofor ms of this family of enzymes. (C) 1999 Elsevier Science Inc.