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

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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.