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:Â
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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gCap39 is phosphorylated. Stimulation by okadaic acid and preferential association with nuclei.
Koji Onoda,Helen L. Yin +1 more
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Studies toward (-)-gymnodimine: concise routes to the spirocyclic and tetrahydrofuran moieties.
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Phosphatases modulate transmission and serotonin facilitation at synapses: studies with the inhibitor okadaic acid.
TL;DR: Phosphatases have a strong modulating influence on synaptic transmission using the permeant phosphatase inhibitor okadaic acid (OA) at frog and crayfish NMJ and in frog NMJs.
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Kinase and phosphatase inhibitors cause rapid alterations in microtubule dynamic instability in living cells.
TL;DR: Results demonstrate that microtubule assembly regulators can be altered rapidly by inhibition of either kinases or phosphatases and suggest that, in the absence of inhibitors, these regulators exist in a dynamic equilibrium between phosphorylated and dephosphorylated states.
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Regulation of native Kv1.3 channels by cAMP-dependent protein phosphorylation
Induk Chung,Lyanne C. Schlichter +1 more
TL;DR: The results support the view that Kv1.3 is regulated in a complex manner by serine/threonine phosphorylation, inasmuch as calphostin C greatly inhibited the current even after Sp-cAMPS, OA, or PKC activation was used to increase proteinosphorylation.
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