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

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 vit...

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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
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description	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.
doi_str_mv	10.1038/337078a0
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A. J ; SIM, A. T. R ; CARLING, D ; HONNOR, R. C ; TSUKITANI, Y ; COHEN, P ; HARDIE, D. G</creator><creatorcontrib>HAYSTEAD, T. A. J ; SIM, A. T. R ; CARLING, D ; HONNOR, R. C ; TSUKITANI, Y ; COHEN, P ; HARDIE, D. G</creatorcontrib><description>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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/337078a0</identifier><identifier>PMID: 2562908</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>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</subject><ispartof>Nature (London), 1989-01, Vol.337 (6202), p.78-81</ispartof><rights>1989 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. 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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
title	Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism
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