title: Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism.
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.
authors.affiliation: Biochemistry Department, The University, Dundee, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Haystead
authors.forename: A T
authors.initials: AT
authors.lastname: Sim
authors.forename: D
authors.initials: D
authors.lastname: Carling
authors.forename: R C
authors.initials: RC
authors.lastname: Honnor
authors.forename: Y
authors.initials: Y
authors.lastname: Tsukitani
authors.forename: P
authors.initials: P
authors.lastname: Cohen
authors.forename: D G
authors.initials: DG
authors.lastname: Hardie
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D002273:Carcinogens; D004988:Ethers, Cyclic; D011506:Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose