Regulation of Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) by protocadherin-γC5 (Pcdh-γC5)

Arch Biochem Biophys. 2015 Nov 1;585:109-120. doi: 10.1016/j.abb.2015.09.014. Epub 2015 Sep 18.

Abstract

Ca(2+)/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 Ca(2+)/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.

Keywords: CaM kinase; N-cadherin; PPM1A/PP2Cα; PPM1F; Protocadherin; γ-secretase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Cadherin Related Proteins
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1 / chemistry
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1 / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • Cytosol / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / metabolism*
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins
  • Signal Transduction

Substances

  • Cadherin Related Proteins
  • Cadherins
  • Gamma-protocadherins
  • Recombinant Fusion Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1
  • Camk1 protein, rat
  • PPM1F protein, mouse
  • Phosphoprotein Phosphatases