Abstract
Protein kinase C(PKC9 is a family of proteins with serine/threonine-specific protein kinase activity which is activated by diacylglycerol(DG)or tumor promot-ing phorbol esters such as TPA. PKC is the only substance identified so far as a cellular receptor for tumor promoting phorbol esters. Thus it is believed that PKC in one of the major component of intra-cellular signalling pathways and is involved in various cellular functions which are mimicked by phorbol esters. Recent molecular cloning and subsequent expression studies as well as biochemi-cal analysis of the PKC molecules revealed two major unexpected facts on the molecular nature of PKC and/or cellular phorbol ester receptor. One is that PKC (originally defined as Ca2+-, phospholipid-activated protein kinase by Nishizuka) is composed of four distinct molecular types, α, βI, βII, γ encoded by three distinct genes. These “conventional PKC molecules share similar enzymatic prop-erties which include substrate specificity and co-factor dependency of the kinase activity. Funthermore they confer phorbol ester receptor activity to intact cells when each cDNA was introduced into cells. The other unexpected fact we found is the presence of PKC-related proteins. PKC-related cDNAs encoded at least three additional members(“novel” PKC, nPKC δ, ε, and ζ) of the PKC family. These “novel” PKC molecules share only part of the sequences with “conventional”PKCs(Cys-rich repeat and kinase). nPKCε is a Ser/Thr-specific protein kinase which is activated by DG or phorbol esters. Furthermore nPKε serves as a phorbol ester receptor. These PKC and nPKC molecules are expressed in a cell-type specific manner, suggesting that they have distinct functional roles in cellular signalling pathways.
