Protein kinase C in fungi-more than just cell wall integrity

Abstract

Human protein kinase C (PKC) isoforms have been implicated in diseases such as Alzheimer's, diabetes and cancers. In contrast to mammals, which have at least nine genes, fungi have only one or two. The yeast Saccharomyces cerevisiae produces only a single Pkc1 and is employed in the study of specific human isozymes, including their susceptibility to pharmacological drugs. Vice versa, the domain structure and regulation of yeast and other fungal PKCs yield insights into the function of human isozymes. Therefore, human PKCs are briefly reviewed herein and related to the yeast enzyme. The latter was originally implicated in the regulation of cell wall synthesis through a conserved MAP kinase pathway, but many more targets have now been described in S. cerevisiae and other fungi. These implicate PKC in the control of such diverse processes as the organization of the actin cytoskeleton, autophagy and apoptosis, nutrient sensing and ribosome biogenesis, cell cycle control, cytokinesis and genetic stability. PKC is a promising target for the development of antifungal drugs against pathogenic fungi such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Thus, fungal PKCs are drawing increased attention and the accumulating literature on the enzymes from different species is summarized herein.

Keywords: PKC; antifungal drugs; cell integrity; fungal pathogens; membrane; signal transduction.