Regulation of Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) by protocadherin-γC5 (Pcdh-γC5)

• Published in: Archives of biochemistry and biophysics 2015-11, Vol.585, p.109-120
• Main Authors: Onouchi, Takashi, Kishino-Kaneko, Yoshimi, Kameshita, Isamu, Ishida, Atsuhiko, Sueyoshi, Noriyuki
• Format: Article
• Language: English
• Subjects: CaM kinase; N-cadherin; PPM1A/PP2Cα; PPM1F; Protocadherin; γ-secretase
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2015.09.014

Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr protein phosphatase that belongs to the PPM family. It is important to identify an endogenous regulator of CaMKP. Using an Escherichia coli two-hybrid screening method, we identified the C-terminal cytoplasmic fragment of protocadherin γ subfamily C5 (Pcdh-γC5), which was generated by intracellular processing, as a CaMKP-binding protein. Dephosphorylation of phosphorylated Ca2+/calmodulin-dependent protein kinase I (CaMKI) by CaMKP was significantly activated by the C-terminal cytoplasmic fragment, Pcdh-γC5(715–944), both in vitro and in cells, suggesting that the C-terminal fragment functions as an endogenous activator of CaMKP. The nuclear translocation of the fragment was blocked by its binding to cytoplasmic CaMKP to form a ternary complex with CaMKI. Taken together, these results strongly suggest that the C-terminal cytoplasmic fragment of Pcdh-γC5 acts as a scaffold for CaMKP and CaMKI to regulate CaMKP activity. These findings may provide new insights into the reversible regulation of CaMKP in cells. •Pcdh-γC5 was identified as a novel binding protein for CaMKP.•CaMKP was activated by a C-terminal cytosolic fragment, Pcdh-γC5(715-944).•Pcdh-γC5 acts as a scaffold for CaMKP and CaMKI to regulate CaMKP activity.•Pcdh-γC5 might act as a physiological activator of CaMKP.