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

详细信息    查看全文

• 作者：Noriyuki Sueyoshi ; Toshihiko Takao ; Takaki Nimura ; Yasunori Sugiyama ; Takamasa Numano ; Yasushi Shigeri ; Takanobu Taniguchi ; Isamu Kameshita ; Atsuhiko Ishida
• 关键词：CaMKP ; CaMKP-N ; CaMK ; PP2C ; Inhibitor ; Permeability ; Calcineurin ; PPM family ; Chemical screening
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2007
• 出版时间：23 November 2007
• 年：2007
• 卷：363
• 期：3
• 页码：715-721
• 全文大小：535 K

文摘

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.