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  • Title: Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism.
    Author: Haystead TA, Sim AT, Carling D, Honnor RC, Tsukitani Y, Cohen P, Hardie DG.
    Journal: Nature; 1989 Jan 05; 337(6202):78-81. PubMed ID: 2562908.
    Abstract:
    Okadaic acid is a polyether derivative of 38-carbon fatty acid, and is implicated as the causative agent of diarrhetic shellfish poisoning. It is a potent tumour promoter that is not an activator of protein kinase C, but is a powerful inhibitor of protein phosphatases-1 and -2A (PP1 and PP2A) in vitro. We report here that okadaic acid rapidly stimulates protein phosphorylation in intact cells, and behaves like a specific protein phosphatase inhibitor in a variety of metabolic processes. Our results indicate that PP1 and PP2A are the dominant protein phosphatases acting on a wide range of phosphoproteins in vivo. We also find that okadaic acid mimics the effect of insulin on glucose transport in adipocytes, which suggests that this process is stimulated by a serine/threonine phosphorylation event.
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