Cholesterol sulfate, an activator of protein kinase C mediating squamous cell differentiation: a review

Activity of protein kinase C (PKC) depends on the interaction with polar he ad-groups of two membrane lipids, i.e., phosphatidylserine and diacylglycer ol, We demonstrated that cholesterol metabolism is directly involved in act ivation of the eta isoform of protein kinase C (PKC eta), which is predomin antly expressed in epithelial tissues in close association with epithelial differentiation. We found that PKC eta was activated by cholesterol sulfate (CS), a metabolite of cholesterol formed during squamous cell differentiat ion. in the presence of CS, phorbol ester only weakly enhanced the activity of PKC eta. CS also activated PKC eta, PKC delta and PKC epsilon in a dose -dependent manner, when assayed using purified recombinant materials. Howev er, when partially purified materials were used from overexpressing normal human keratinocytes, only PKC eta was activated by CS among the isoforms ex amined. All the existing lines of evidence, mainly supplied from our labora tory, suggest that CS is involved in a signal transduction of squamous cell differentiation and thereby modifying squamous cell carcinogenesis. (C) 20 00 Elsevier Science B,V. All rights reserved.