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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tachibana, K. et al. J. Am. chem. Soc. 103, 2469–2471 (1981).
Murata, M., Shimatani, M., Sugitani, H., Oshima, Y. & Yasumoto, T. Bull. Japan Soc. scient. Fish. 48, 549–552 (1982).
Suganuma, M. et al. Proc. natn, Acad. Sci. U.S.A. 85, 1768–1777 (1988).
Bialojan, C. & Takai, A. Biochem. J. 256, 283–290 (1988).
Hescheler, J., Mieskes, G., Ruegg, J. C., Takai, A. & Trautwein, W. Pflugers Arch. ges. Physiol. 412, 248–252 (1988).
Ozaki, H., Kohama, K., Nonomura, Y., Shibata, S. & Karaki, H. Naunyn-Schmiedebergs Arch. Pharmak. 335, 356–358 (1987).
Takai, A., Bialojan, C., Troschka, M. & Ruegg, J. C. FEBS Lett. 217, 81–84 (1987).
Berndt, N. et al. FEBS Lett. 223, 340–346 (1987).
Ingebritsen, T. S. & Cohen, P. Science 221, 331–338 (1983).
Cohen, P. Proc. R. Soc. B 234, 115–144 (1988).
Cohen, P. A. Rev. Biochem. (in the press).
Pilkis, S. J., El-Maghrabi, M. R. & Claus, J. H. A. Rev. Biochem. 57, 755–783 (1988).
Sim, A. T. R. & Hardie, D. G. FEBS Lett. 233, 294–298 (1988).
Cohen, P. Molec. Asp. Cell. Reg. Vol. 5 (eds Cohen, P. & Klee, C. B.) 123–144 (Elsevier Biomedical, Amsterdam, 1988).
Cohen, P. in The Enzymes 3rd edn Vol. 17 (eds Boyer, P. D. & Krebs, E. G.), 361–392 (Academic, Orlando, 1987).
Haystead, T. A. J., Campbell, D. G. & Hardie, D. G. Eur. J. Biochem. 175, 347–354 (1988).
Honnor, R. C., Dhillon, G. S. & Londos, C. J. biol. Chem. 260, 15122–15129 (1985).
Munday, M. R., Campbell, D. G., Carling, D. & Hardie, D. G. Eur. J. Biochem. 175, 331–338 (1988).
Gibbs, E. M., Allard, W. J. & Lienhard, G. E. J. biol. Chem. 261, 16597–16603 (1986).
Haystead, T. A. J. & Hardie, D. G. Biochem. J. 234, 279–284 (1986).
Holland, R., Witters, L. A. & Hardie, D. G. Eur. J. Biochem. 140, 325–333 (1984).
Laemmli, U. K. Nature 227, 680–685 (1970).
Exton, J. H. & Park, C. R. J. biol. Chem. 244, 1424–1433 (1968).
Haystead, T. A. J. & Hardie, D. G. Eur. J. Biochem. 175, 339–345 (1988).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haystead, T., Sim, A., Carling, D. et al. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism. Nature 337, 78–81 (1989). https://doi.org/10.1038/337078a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/337078a0
This article is cited by
-
Equivocal, explicit and emergent actions of PKC isoforms in cancer
Nature Reviews Cancer (2021)
-
Partners in crime: POPX2 phosphatase and its interacting proteins in cancer
Cell Death & Disease (2020)
-
Magnetic titanium dioxide nanomaterial modified with hydrophilic dicarboxylic ligand for effective enrichment and separation of phosphopeptides and glycopeptides
Microchimica Acta (2020)
-
Magnetite nanoparticles coated with mercaptosuccinic acid-modified mesoporous titania as a hydrophilic sorbent for glycopeptides and phosphopeptides prior to their quantitation by LC-MS/MS
Microchimica Acta (2019)
-
Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology
The Journal of Physiological Sciences (2018)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.