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Differential effects of suramin on protein kinase C isoenzymes. A novel tool for discriminating protein kinase C activities
Author(s) -
Gschwendt Michael,
Kittstein Walter,
Johannes Franz-Josef
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01530-5
Subject(s) - suramin , protein kinase c , chelerythrine , autophosphorylation , biochemistry , isozyme , chemistry , kinase , microbiology and biotechnology , biology , protein kinase a , in vitro , enzyme
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 α, β, and γ. Here we report on a differential effect of suramin on PKCμ and various PKC isoforms representing the cPKC, nPKC, and aPKC group of the PKC family. In the absence of any cofactors suramin activates all PKC isoforms in the order of aPKCζ≫PKCμ>cPKC, nPKCδ. As judged by the V max / K M ratios (0.5 for PKCμ and 2.2 for PKCζ) the substrate syntide 2 is phosphorylated by suramin‐activated PKCζ around four times more effectively than by suramin‐activated PKCμ. Suramin‐activated PKCμ behaves like that activated by phosphatidylserine and the phorbol ester TPA regarding autophosphorylation and differential inhibition by the PKC inhibitors Gö 6976 and Gö 6983. In the presence of activating cofactors, such as phosphatidylserine and TPA or cholesterol sulfate (for PKCζ), the activity of the aPKCζ is further stimulated, PKCμ is not significantly affected, and the cPKCs and the nPKCδ 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.