Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism

T. A.J. Haystead, A. T.R. Sim, D. Carling, R. C. Honnor, Y. Tsukitani, P. Cohen, D. G. Hardie

    Research output: Contribution to journalLetter

    681 Citations (Scopus)

    Abstract

    Okadaic acid is a polyether derivative of 38-carbon fatty acid1, and is implicated as the causative agent of diarrhetic shellfish poisoning2. It is a potent tumour promoter that is not an activator of protein kinase C (ref. 3), but is a powerful inhibitor of protein phosphatases-1 and -2A (PP1 and PP2A) in vitro4,5. 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.

    Original languageEnglish
    Pages (from-to)78-81
    Number of pages4
    JournalNature
    Volume337
    Issue number6202
    DOIs
    Publication statusPublished - 5 Jan 1989

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