Protein Kinase C Regulation by Sphingosine/Lysosphingolipids

Investigations on protein kinase C., actually a super-family of seven or more closely related kinases (Ono et al. 1988), have led to connections between diverse areas of biology as a consequence of its central role in signal transduction processes (Nishizuka 1986) and its intimate regulation by cellular lipids and breakdown products of these lipids. This paper describes, in part, these biological connections, with emphasis on the role of protein kinase C in cell growth, regulation, differentiation, and oncogenesis. The main emphasis of the paper is on the connections and involvement of cellular lipids, both glycerolipids (Bell 1986) and sphingolipids (Hannun et al. 1986b), in the regulation of protein kinase C. The discovery that sphingolipid breakdown products inhibit protein kinase C has led to a unifying hypothesis with broad imphcations for cell regulation, pathogenesis, and medicine (Hannun et al. 1986b; Hannun and Bell 1987; Bell et al. 1988). The insights afforded...