Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism |
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Authors: | T A Haystead A T Sim D Carling R C Honnor Y Tsukitani P Cohen D G Hardie |
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Affiliation: | Biochemistry Department, The University, Dundee, UK. |
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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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