[show abstract][hide abstract] ABSTRACT: Activity of protein kinase C (PKC) depends on the interaction with polar head-groups of two membrane lipids, i.e., phosphatidylserine and diacylglycerol. We demonstrated that cholesterol metabolism is directly involved in activation of the η isoform of protein kinase C (PKCη), which is predominantly expressed in epithelial tissues in close association with epithelial differentiation. We found that PKCη was activated by cholesterol sulfate (CS), a metabolite of cholesterol formed during squamous cell differentiation. In the presence of CS, phorbol ester only weakly enhanced the activity of PKCη. CS also activated PKCη, PKCδ and PKCϵ in a dose-dependent manner, when assayed using purified recombinant materials. However, when partially purified materials were used from overexpressing normal human keratinocytes, only PKCη was activated by CS among the isoforms examined. All the existing lines of evidence, mainly supplied from our laboratory, suggest that CS is involved in a signal transduction of squamous cell differentiation and thereby modifying squamous cell carcinogenesis.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 05/2000; · 3.90 Impact Factor