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

T. A.J. Haystead; A. T.R. Sim; D. Carling; R. C. Honnor; Y. Tsukitani; P. Cohen; D. G. Hardie

doi:10.1038/337078a0

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

T. A.J. Haystead
, A. T.R. Sim
, D. Carling
, R. C. Honnor
, Y. Tsukitani
, P. Cohen
, D. G. Hardie

Research output: Contribution to journal › Letter › peer-review

796 Citations (Scopus)

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 vitro^4,5. 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.

Original language	English
Pages (from-to)	78-81
Number of pages	4
Journal	Nature
Volume	337
Issue number	6202
DOIs	https://doi.org/10.1038/337078a0
Publication status	Published - 5 Jan 1989

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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 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.",

author = "Haystead, \{T. A.J.\} and Sim, \{A. T.R.\} and D. Carling and Honnor, \{R. C.\} and Y. Tsukitani and P. Cohen and Hardie, \{D. G.\}",

year = "1989",

month = jan,

day = "5",

doi = "10.1038/337078a0",

language = "English",

volume = "337",

pages = "78--81",

journal = "Nature",

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TY - JOUR

T1 - Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism

AU - Haystead, T. A.J.

AU - Sim, A. T.R.

AU - Carling, D.

AU - Honnor, R. C.

AU - Tsukitani, Y.

AU - Cohen, P.

AU - Hardie, D. G.

PY - 1989/1/5

Y1 - 1989/1/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0024592297

U2 - 10.1038/337078a0

DO - 10.1038/337078a0

M3 - Letter

C2 - 2562908

AN - SCOPUS:0024592297

SN - 0028-0836

VL - 337

SP - 78

EP - 81

JO - Nature

JF - Nature

IS - 6202

ER -

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

Abstract

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