Functional processing of nuclear Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP-N): Evidence for a critical role of proteolytic processing in the regulation of its catalytic activity, subcellular localization and substrate targeting in vivo
- Authors
- Sueyoshi, N., Nimura, T., Onouchi, T., Baba, H., Takenaka, S., Ishida, A., and Kameshita, I.
- ID
- ZDB-PUB-111129-2
- Date
- 2012
- Source
- Archives of biochemistry and biophysics 517(1): 43-52 (Journal)
- Registered Authors
- Keywords
- CaMKP-N, functional processing, proteasome, ubiquitin
- MeSH Terms
-
- Animals
- Brain/metabolism
- Catalytic Domain
- Cell Line
- Mice
- Phosphoprotein Phosphatases/analysis*
- Phosphoprotein Phosphatases/metabolism*
- Proteasome Endopeptidase Complex/metabolism
- Proteasome Inhibitors
- Proteolysis
- Rats
- Zebrafish/metabolism*
- Zebrafish Proteins/analysis*
- Zebrafish Proteins/metabolism*
- PubMed
- 22100705 Full text @ Arch. Biochem. Biophys.
Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP) and its nuclear homolog CaMKP-N are Ser/Thr protein phosphatases that belong to the PPM family. These phosphatases are highly specific for multifunctional CaM kinases and negatively regulate their activities. CaMKP-N is only expressed in the brain and specifically localized in the nucleus. In this study, we found that zebrafish CaMKP-N (zCaMKP-N) underwent proteolytic processing in both the zebrafish brain and Neuro2a cells. In Neuro2a cells, the proteolytic processing was effectively inhibited by the proteasome inhibitors MG-132, Epoxomicin, and Lactacystin, suggesting that the ubiquitin–proteasome pathway was involved in this processing. Using MG-132, we found that the proteolytic processing changed the subcellular localization of zCaMKP-N from the nucleus to the cytosol. Accompanying this change, the cellular targets of zCaMKP-N in Neuro2a cells were significantly altered. Furthermore, we obtained evidence that the zCaMKP-N activity was markedly activated when the C-terminal domain was removed by the processing. Thus, the proteolytic processing of zCaMKP-N at the C-terminal region regulates its catalytic activity, subcellular localization and substrate targeting in vivo.