Protein kinase C in cellular transformation: a valid target for therapy?

Abstract

The protein kinase C (PKC) family of serine/threonine protein kinases share structural homology, while exhibiting substantial functional diversity. PKC isoforms are ubiquitously expressed in tissues which makes it difficult to define roles for individual isoforms, with complexity compounded by the finding that PKC isoforms can co-operate with or antagonize other PKC family members. A number of studies suggest the involvement of PKC family members in regulating leukaemic cell survival and proliferation. Chronic lymphocytic leukaemia (CLL), the most common leukaemia in the Western world, exhibits dysregulated expression of PKC isoforms, with recent reports indicating that PKCβ and δ play a critical role in B-cell development, due to their ability to link the B-cell receptor (BCR) with downstream signalling pathways. Given the prognostic significance of the BCR in CLL, inhibition of these BCR/PKC-mediated signalling pathways is of therapeutic relevance. The present review discusses the emerging role of PKC isoforms in the pathophysiology of CLL and assesses approaches that have been undertaken to modulate PKC activity.