tors, phorbol esters, okadaic acid, or protein synthesis inhibitors, the early-response genes, which include c-fos and c-jun, are rapidly induced. [1],[2],[3] It is a very weak inhibitor of PP2B (IC50 > 2 μM) and does not inhibit PP2C or other phosphatases. Okadaic acid (OA) is a specific and potent protein phosphatase inhibitor and tumor promoter. The study showed that okadaic acid is cytotoxic at 10 nM with an IC50 of 100 nM in U-937 cells. The earliest growth factor- and phorbol ester-stimulated nuclear signaling events concomitant with proto-oncogene in- Elife 8:N/A (2019). Okadaic acid (10 nM) inhibited PP-2A activity and okadaic acid (100 nM) inhibited both PP-2A and PP-1 activity. In confluent rabbit lens epithelial cells (RLECs), okadaic acid (100 nM) significantly induced cell apoptosis. Okadaic acid eliminate metazoan symbionts/parasites by apoptosis. Okadaic acid (0.05 and 0.5 nmol) at a survival time of 30 min significantly increased c-fos mRNA hybridization signals in the striatum in a dose-dependent manner. Okadaic acid is extracted from black sponges of the genus Halichondria. Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are activated in NIH3T3 cells exposed to okadaic acid. Okadaic acid (OA) is a specific and potent protein phosphatase inhibitor and tumor promoter. Okadaic acid (OA)‑induced neurotoxicity may be considered a novel tool used to study Alzheimer's disease (AD) pathology, and may be helpful in the development of a novel therapeutic approach. The CVDE assay and mitochondrial dehydrogenase … Ravindran J, Gupta N, Agrawal M, Bala Bhaskar AS, Lakshmana Rao PV (2011) Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism. The present study establishes the role of reactive oxygen species (ROS) and mitogen activated protein kinases in cell death induced by okadaic acid.

- Mechanism of Action & Protocol. (1999) Biochem J 341 ( Pt 3), 839-45. The antibodies against phospho-Rb(S807/811) (Cell Signaling), which do not recognize Rb phosphorylated at other sites, as indicated by the manufacturer, were overlaid onto the cells.

IC 50 values for inhibitory activity against PP1 are approximately 2 nM.
The study showed that okadaic acid is cytotoxic at 10 nM with an IC50 of 100 nM in U-937 cells. Okadaic acid is a non-comepetitive, selective and reversible serine/threonine-specific protein phosphatases 1 (PP1), PP2A and PP3 inhibitor with IC50s of 10-15 nM, 0.5 nM and 4 nM, respectively. Application Okadaic acid from Prorocentrum concavum has been used as a phosphatase inhibitor: • to inhibit protein phosphatase 2 in spermatocytes culture • to treat SH-SY5Y cells to prevent dephosphorylation to maintain tau (1989) Biochem Biophys Res Commun 159, 871-7. MST1 and MST2 work as core kinases of the Hippo pathway and their activities depend on the autophosphorylation, which is negatively regulated by protein phosphatase 2A (PP2A).

Shirish Shenolikar, Matthew H. Brush, in Handbook of Cell Signaling (Second Edition), 2010. Okadaic acid is a marine sponge toxin which potently inhibits certain serine/threonine protein phosphatases. Okadaic acid at 0.05 nmol significantly increased pCREB and pElk-1. Also, okadaic acid induced the expression of p53 and bax, which are necessary for the apoptotic programs. Since both phosphorylation and dephosphorylation of proteins are inevitable process in cell signaling pathway, amino acid sequences for the catalytic subunit of protein phosphatases are highly conserved. The present study establishes the role of reactive oxygen species (ROS) and mitogen activated protein kinases in cell death induced by okadaic acid. As shown by Western blot, treatment of cells with 100 nM Calyculin A for 30 minutes induces threonine phosphorylation, detected by Phospho-Threonine-Polyclonal Antibody #9381. Okadaic acid is a polyether fatty acid. 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).
Unlike Okadaic acid, which reduces PP2A activity but has little effect on PP1 activity, Calyculin A inhibits both phosphatases (1).

Resjö, S. et al. The Hippo pathway is a newly emerging signaling that functions as a tumor suppressor. Okadaic acid, responsible for human diarrheretic shellfish poisoning, was first identified as a toxin concentrated by marine sponges, and functions as a potent inhibitor of several eukaryotic protein serine/threonine phosphatases. PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins. Potent inhibitor of protein phosphatases, especially the PP-1 and PP-2 classes, in numerous cell types.


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