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

• Published in: Nature (London) 1989-01, Vol.337 (6202), p.78-81
• Main Authors: HAYSTEAD, T. A. J, SIM, A. T. R, CARLING, D, HONNOR, R. C, TSUKITANI, Y, COHEN, P, HARDIE, D. G
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - metabolism; Acids; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Biological and medical sciences; Carcinogens - pharmacology; Cell physiology; Ethers, Cyclic - pharmacology; Fatty acids; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Liver - drug effects; Liver - metabolism; Molecular and cellular biology; Okadaic Acid; phosphatase-1; phosphatase-2A; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphorylation; Poisoning; Proteins; Proteins - metabolism; Rats; Responses to growth factors, tumor promotors, other factors; Shellfish; tumors
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/337078a0

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.