12-Deoxyphorbol-13-O-phenylacetate-20-acetate is not protein kinase C-β isozyme-selective in vivo

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Abstract
The phorbol ester, 12-deoxyphorbol-13-O-phenylacetate-20-acetate (DOPPA) has been shown to activate specifically the protein kinase C (PKQ-β1 isozyme in vitro (1). We have investigated the potential of DOPPA as a PKC-β½ isozyme-specific agonist hi intact cells, employing U937 cells, which express β½, ε and ζ PKC and in Swiss 3T3 cells which lack PKC-β½ but express α, δ, ε and ζ PKC. Immunoblot analysis with isozyme-specific antibodies indicated that DOPPA can mediate the subcellular redistribution and down-modulation of all endogenous PKC isozymes (except PKC-ζ) in both U937 and Swiss 3T3 cells. Prolonged treatment (>6 h) of cultures in down-modulation studies is complicated by the metabolism of DOPPA to 12-deoxyphorbol-13-phenylacetate (DOPP), a compound which activates all PKC isozymes tested in vitro (Ryves,WJ. et al. (1991) FEBS Lett., 288, 5–9). Nevertheless, because DOPPA induced rapid and dose-dependent phosphorylation of p80 in cells which do not express PKC-β, p80 phosphorylation in Swiss 3T3 cells indicates that DOPPA can activate a non-β PKC in vivo. The data suggest that DOPPA cannot be used as a PKC-β-selective agonist in intact cell studies.

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