Functional processing of nuclear Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP-N): evidence for a critical role of proteolytic processing in the …

N Sueyoshi, T Nimura, T Onouchi, H Baba… - Archives of biochemistry …, 2012 - Elsevier
N Sueyoshi, T Nimura, T Onouchi, H Baba, S Takenaka, A Ishida, I Kameshita
Archives of biochemistry and biophysics, 2012Elsevier
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 …
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.
Elsevier