Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics
Corinna Bialojan,Akira Takai +1 more
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Kinetic studies showed that okadaic acid acts as a non-competitive or mixed inhibitor on the okadaIC acid-sensitive enzymes.Abstract:
The inhibitory effect of a marine-sponge toxin, okadaic acid, was examined on type 1, type 2A, type 2B and type 2C protein phosphatases as well as on a polycation-modulated (PCM) phosphatase. Of the protein phosphatases examined, the catalytic subunit of type 2A phosphatase from rabbit skeletal muscle was most potently inhibited. For the phosphorylated myosin light-chain (PMLC) phosphatase activity of the enzyme, the concentration of okadaic acid required to obtain 50% inhibition (ID50) was about 1 nM. The PMLC phosphatase activities of type 1 and PCM phosphatase were also strongly inhibited (ID50 0.1-0.5 microM). The PMCL phosphatase activity of type 2B phosphatase (calcineurin) was inhibited to a lesser extent (ID50 4-5 microM). Similar results were obtained for the phosphorylase a phosphatase activity of type 1 and PCM phosphatases and for the p-nitrophenyl phosphate phosphatase activity of calcineurin. The following phosphatases were not affected by up to 10 microM-okadaic acid: type 2C phosphatase, phosphotyrosyl phosphatase, inositol 1,4,5-trisphosphate phosphatase, acid phosphatases and alkaline phosphatases. Thus okadaic acid had a relatively high specificity for type 2A, type 1 and PCM phosphatases. Kinetic studies showed that okadaic acid acts as a non-competitive or mixed inhibitor on the okadaic acid-sensitive enzymes.read more
Citations
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Requirement of protein phosphatase 2A for recruitment of IQGAP1 to Rac‐bound β1 integrin
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Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization
TL;DR: In this article, the authors used suppression subtractive hybridization in SHSY5Y cells to identify genes that are differentially expressed after OA exposure for different times (3, 24 and 48 h).
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Signaling events following the interaction of the neuronal adhesion molecule F3 with the N-terminal domain of tenascin-R.
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Phosphatase Is Responsible for Run Down, and Probably G Protein-mediated Inhibition of Inwardly Rectifying K + Currents in Guinea Pig Chromaffin Cells
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Comparative studies of the actin cytoskeleton response to maitotoxin and okadaic acid.
TL;DR: An MTX- like effect which is distinct from an OA-like effect is defined, in both cases the amount of F-actin diminished at doses that did not affect cell viability.
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