Inhibitors of the Ca(2+)/calmodulin-dependent protein kinase phosphatase family (CaMKP and CaMKP-N)
- Authors
- Sueyoshi, N., Takao, T., Nimura, T., Sugiyama, Y., Numano, T., Shigeri, Y., Taniguchi, T., Kameshita, I., and Ishida, A.
- ID
- ZDB-PUB-140211-1
- Date
- 2007
- Source
- Biochemical and Biophysical Research Communications 363(3): 715-721 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Blotting, Western
- Calcium-Calmodulin-Dependent Protein Kinases/metabolism*
- Catalysis/drug effects
- Cell Line, Tumor
- Coloring Agents/chemistry
- Coloring Agents/pharmacology
- Enzyme Inhibitors/chemistry*
- Enzyme Inhibitors/pharmacology*
- Evans Blue/chemistry
- Evans Blue/pharmacology
- Kinetics
- Phosphoprotein Phosphatases/antagonists & inhibitors*
- Phosphoprotein Phosphatases/genetics
- Phosphoprotein Phosphatases/metabolism
- Phosphoproteins/metabolism
- Phosphorylation/drug effects
- Substrate Specificity
- Transfection
- Trypan Blue/chemistry
- Trypan Blue/pharmacology
- PubMed
- 17897624 Full text @ Biochem. Biophys. Res. Commun.
Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP) and its nuclear isoform CaMKP-N are unique Ser/Thr protein phosphatases that negatively regulate the Ca2+/calmodulin-dependent protein kinase (CaMK) cascade by dephosphorylating 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.