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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TLDR
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 PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells.
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Mechanism of the stimulatory action of okadaic acid on lipolysis in rat fat cells
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Inhibition of alkaline phosphatase activity by okadaic acid, a protein phosphatase inhibitor.
TL;DR: Kinetic analysis of ALP from Escherichia coli, human placental and calf intestinal ALP has shown that OA acts as a non-competitive inhibitor of ALP, which suggests a putative role of ALP in the phosphorylation status, through regulation of the phospharylation/dephosphorylation equilibrium of proteins with phosphoseryl or phosphothreonyl residues.
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Reversible activation of glutamate transport in rat brain glia by protein kinase C and an okadaic acid-sensitive phosphoprotein phosphatase.
TL;DR: Results demonstrate that glial EAAT can be regulated by multiple phosphorylation processes and are consistent with previous work on heterogenous EAA transporters.
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Modulation of the skeletal muscle ryanodine receptor by endogenous phosphorylation of 160/150-kda proteins of the sarcoplasmic reticulum
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