Differential effects of suramin on protein kinase C isoenzymes. A novel tool for discriminating protein kinase C activities

Suramin, a hexasulfonated naphthylurea, is known to induce differentiation and inhibit proliferation, angiogenesis, and development of tumors, It has also been shown to suppress the activity of the protein kinase C (PKC) isoenzymes alpha, beta, and gamma. Here we report on a differential effect of suramin on PKC mu and various PKC isoforms representing the cPKC nPKC, and aPKC group of the PRC family, In the absence of any cofactors suramin activates all PKC isoforms in the order of aPKC-zeta much greater than PKC mu > cPKC, nPKC delta, As judged by the V-max/K-M ratios (0.5 for PKC mu and 2.2 for PKC zeta) the substrate syntide 2 is phosphorylated by suramin-activated PKC zeta around four times more effectively than by suramin-activated PKC mu, Suramin-activated PKC mu behaves like that activated by phosphatidylserine and the phorbol ester TPA regarding autophosphorylation and differential inhibition by the PKC inhibitors Go 6976 and Go 6983, In the presence of activating cofactors, such as phosphatidylserine and TPA or cholesterol sulfate (for PKC zeta), the activity of the aPKC zeta is further stimulated, PKC mu is not significantly affected, and the cPKCs and the nPKC delta are strongly inhibited by suramin. The differential action of suramin on PKC isoenzymes might play a role in some of its biological effects, as for instance inhibition of proliferation and tumor development. Moreover, due to this property suramin will possibly be a valuable tool for discriminating the activities of PKC isoenzymes in vitro and in vivo. (C) 1998 Federation of European Biochemical Societies.