Okadaic acid is a marine sponge toxin which potently inhibits certain serine/threonine protein phosphatases. This cell permeable inhibitor targets the multiple isoforms of PP1 (IC50 = 10-50 nM), both isoforms of PP2A (IC50 = 0.5 nM) and PP3 (IC50 = 4 nM).[1],[2],[3] It is a very weak inhibitor of PP2B (IC50 > 2 μM) and does not inhibit PP2C or other phosphatases.[1],[3 ]Presumably through these actions, okadaic acid is a potent carcinogen and induces tau phosphorylation.[4],[5] In sponge, okadaic acid plays a role in defense, inducing apoptosis in symbiotic or parasitic annelids.[6]
Reference:
[1]. Bialojan, C., and Takai, A. Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics. Biochemistry Journal 256, 283-290 (1988).
[2]. Gupta, V., Ogawa, A.K., Du, X., et al. A model for binding of structurally diverse natural product inhibitors of protein phosphatases PP1 and PP2A. Journal of Medicinal Chemistry 40, 3199-3206 (1997).
[3]. McCluskey, A., Sim, A.T.R., and Sakoff, J.A. Serine-threonine protein phosphatase inhibitors: Development of potential therapeutic strategies. Journal of Medicinal Chemistry 45(6), 1151-1175 (2002).
[4]. Suganuma, M., Fujiki, H., Suguri, H., et al. Okadaic acid: An additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proceedings of the National Academy of Sciences of the United States of America 85, 1768-1771 (1988).
[5]. Zhang, Z., and Simpkins, J.W. Okadaic acid induces tau phosphorylation in SH-SY5Y cells in an estrogen-preventable manner. Brain Research 1345, 176-181 (2010).
[6]. Schröder, H.C., Breter, H.J., Fattorusso, E., et al. Okadaic acid, an apoptogenic toxin for symbiotic/parasitic annelids in the demosponge Suberites domuncula. Applied and Environmental Microbiology 72(7), 4907-4916 (2006).