Okadaic Acid, Useful Tool for Studying Cellular Processes

Fernández, José J.; Candenas, M. L.; Souto, Marı́a L.; Trujillo, Marco; Norte, Manuel

doi:10.2174/0929867023371247

Cited by 143 publications

(79 citation statements)

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“…Calyculin A inhibits protein phosphatase 1 (PP1; IC 50 0.3-0.7 nM) and protein phosphatase 2a (PP2a; IC 50 0.2-1 nM) at similar concentrations (Fernandez et al, 2002). However, ϳ50-fold higher concentrations of okadaic acid are required to inhibit PP1 (IC 50 20 nM) compared with PP2a (IC 50 0.2-1 nM).…”

Section: Figure 3 Time Course Of Cpeb Phosphorylation In Neurons Stimentioning

confidence: 99%

“…However, ϳ50-fold higher concentrations of okadaic acid are required to inhibit PP1 (IC 50 20 nM) compared with PP2a (IC 50 0.2-1 nM). Neither phosphatase inhibitor has any significant effect on calcineurin, PP2b (Fernandez et al, 2002). We took advantage of these protein phosphatase inhibitors and their IC 50 values to identify the protein phosphatase that regulates CPEB in hippocampal neurons.…”

Section: Figure 3 Time Course Of Cpeb Phosphorylation In Neurons Stimentioning

confidence: 99%

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Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Atkins¹,

Nozaki²,

Shigeri³

et al. 2004

J. Neurosci.

137

131

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Phosphorylation of cytoplasmic polyadenylation element binding protein (CPEB) regulates protein synthesis in hippocampal dendrites. CPEB binds the 3Ј untranslated region (UTR) of cytoplasmic mRNAs and, when phosphorylated, initiates mRNA polyadenylation and translation. We report that, of the protein kinases activated in the hippocampus during synaptic plasticity, calcium/calmodulindependent protein kinase II (CaMKII) robustly phosphorylated the regulatory site (threonine 171) in CPEB in vitro. In postsynaptic density fractions or hippocampal neurons, CPEB phosphorylation increased when CaMKII was activated. These increases in CPEB phosphorylation were attenuated by a specific peptide inhibitor of CaMKII and by the general CaM-kinase inhibitor KN-93. Inhibitors of protein phosphatase 1 increased basal CPEB phosphorylation in neurons; this was also attenuated by a CaM-kinase inhibitor. To determine whether CaM-kinase activity regulates CPEB-dependent mRNA translation, hippocampal neurons were transfected with luciferase fused to a 3Ј UTR containing CPE-binding elements. Depolarization of neurons stimulated synthesis of luciferase; this was abrogated by inhibitors of protein synthesis, mRNA polyadenylation, and CaMKII. These results demonstrate that CPEB phosphorylation and translation are regulated by CaMKII activity and provide a possible mechanism for how dendritic protein synthesis in the hippocampus may be stimulated during synaptic plasticity.

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Section: Figure 3 Time Course Of Cpeb Phosphorylation In Neurons Stimentioning

confidence: 99%

Section: Figure 3 Time Course Of Cpeb Phosphorylation In Neurons Stimentioning

confidence: 99%

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Atkins¹,

Nozaki²,

Shigeri³

et al. 2004

J. Neurosci.

137

131

View full text Add to dashboard Cite

show abstract

“…The results showed that with control incubation, tau was dephosphorylated at Thr212, Ser262, and Ser396 by protein phosphatases, while OA, a potent protein phosphatase inhibitor, prevented the dephosphorylation of tau at 10 nmol/L, a concentration that only inhibits PP2A [19] .…”

Section: Pp2a In Vitromentioning

confidence: 96%

“…In vitro, tau is gradually dephosphorylated by many serine/threonine protein phosphatases, of which PP2A contributes the major part [7] . OA is a potent inhibitor of protein phosphatase, and only inhibits PP2A when used at 10 nmol/L in vitro [19] .…”

Section: Pp2amentioning

confidence: 99%

Zinc binds to and directly inhibits protein phosphatase 2A in vitro

et al. 2015

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Zinc induces protein phosphatase 2A (PP2A) inactivation and tau hyperphosphorylation through PP2A (tyrosine 307) phosphorylation in cells and the brain, but whether Zn 2+ has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn 2+ on PP2A and their direct interaction in vitro. The results showed that Zn 2+ mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration (10 μmol/L) of Zn 2+ inhibited PP2A directly. Further Zn 2+ -IDA-agarose affinity binding assays showed that Zn 2+ bound to and inhibited PP2Ac but not PP2Ac or PP2Ac . Taken together, Zn 2+ inhibits PP2A directly through binding to PP2Ac in vitro.

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“…4, lanes 3-5). These data suggested that Evans Blue, Chicago Sky Blue, and Oxamine Blue can be effectively incorporated into cells to [24,25]. For PPM phosphatases, however, only two compounds have been so far reported as specific inhibitors.…”

Section: Effects Of the Inhibitors On The Phosphatase Activity Of Cammentioning

confidence: 99%

Inhibitors of the Ca2+/calmodulin-dependent protein kinase phosphatase family (CaMKP and CaMKP-N)

Sueyoshi

Takao

Nimura

et al. 2007

Biochemical and Biophysical Research Communications

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multifunctional CaMKI, II, and IV. However, the lack of specific inhibitors of these phosphatases has hampered studies on these enzymes in vivo. In an attempt to obtain specific inhibitors, we searched inhibitory compounds and found that Evans Blue and Chicago Sky Blue 6B served as effective inhibitors for CaMKP. These compounds also inhibited CaMKP-N, but inhibited neither protein phosphatase 2C, another member of PPM family phosphatase, nor calcineurin, a typical PPP family phosphatase. The minimum structure required for the inhibition was 1-amino-8-naphthol-4-sulfonic acid.When Neuro2a cells cotransfected with CaMKIV and CaMKP-N were treated with these compounds, the dephosphorylation of CaMKIV was strongly suppressed, suggesting that these compounds could be used as potent inhibitors of CaMKP and CaMKP-N in vivo as well as in vitro.

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Okadaic Acid, Useful Tool for Studying Cellular Processes

Cited by 143 publications

References 0 publications

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Zinc binds to and directly inhibits protein phosphatase 2A in vitro

Inhibitors of the Ca2+/calmodulin-dependent protein kinase phosphatase family (CaMKP and CaMKP-N)

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