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
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Inhibition of a p38/Stress-Activated Protein Kinase-2-Dependent Phosphatase Restores Function of IL-1 Receptor-Associated Kinase-1 and Reverses Toll-Like Receptor 2- and 4-Dependent Tolerance of Macrophages
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Hypoxia activated Smad3-specific dephosphorylation by PP2A
Pekka T. Heikkinen,Marika Nummela,Suvi-Katri Leivonen,Jukka Westermarck,Caroline S. Hill,Veli-Matti Kähäri,Panu Jaakkola,Panu Jaakkola +7 more
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Mitotic arrest with anti-microtubule agents or okadaic acid is associated with increased glycoprotein terminal GlcNAc's
Chih-Fong Chou,M. B. Omary +1 more
TL;DR: In vitro galactosylation is used to show that increased terminal GlcNAc's is a general phenomenon that occurs in glycoproteins isolated from nuclear and plasma membrane fractions after cells are arrested in mitosis using colcemid, nocodazole, or okadaic acid.
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Functional assays in marine biotoxin detection.
TL;DR: The achievement of a "systemic functional assay for marine biotoxins" does not appear to be at hand, but its inclusion among the foreseeable events is fully justified by the new research tools and approaches which have become available for the high throughput analysis of entire molecular domains at the cellular level.
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Okadaic acid induces morphological changes, apoptosis and cell cycle alterations in different human cell types
TL;DR: Increases in the apoptosis rate were obtained in all the cells treated in the absence of S9 fraction, accompanied by increases in caspase 3 activation, suggesting that apoptosis induced by OA is a casp enzyme 3-dependent process.
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