Interaction of p130 with, and Consequent Inhibition of, the Catalytic Subunit of Protein Phosphatase 1α

Kenji Yoshimura, Hiroshi Takeuchi, Osamu Sato, Kiyoshi Hidaka, Naoko Doira, Miho Terunuma, Kae Harada, Yasuo Ogawa, Yushi Ito, Takashi Kanematsu, Masato Hirata

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Abstract

The protein p130 was originally isolated from rat brain as an inositol 1,4,5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C-δ1 but which lacks phospholipase C activity. Yeast two-hybrid screening of a human brain cDNA library for clones that encode proteins that interact with p130 has now led to the identification of the catalytic subunit of protein phosphatase 1α (PP1cα) as a p130-binding protein. The association between p130 and PP1cα was also confirmed in vitro by an overlay assay, a "pull-down" assay, and surface plasmon resonance analysis. The interaction of p130 with PP1cα resulted in inhibition of the catalytic activity of the latter in a p130 concentration-dependent manner. Immunoprecipitation and immunoblot analysis of COS-1 cells that stably express p130 and of mouse brain extract with antibodies to p130 and to PP1cα also detected the presence of a complex of p130 and PP1cα. The activity of glycogen phosphorylase, which is negatively regulated by dephosphorylation by PP1cα, was higher in COS-1 cells that stably express p130 than in control COS-1 cells. These results suggest that, in addition to its role in inositol 1,4,5-trisphosphate and Ca2+ signaling, p130 might also contribute to regulation of protein dephosphorylation through its interaction with PP1cα.

Original languageEnglish
Pages (from-to)17908-17913
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
Publication statusPublished - Jan 25 2001

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yoshimura, K., Takeuchi, H., Sato, O., Hidaka, K., Doira, N., Terunuma, M., ... Hirata, M. (2001). Interaction of p130 with, and Consequent Inhibition of, the Catalytic Subunit of Protein Phosphatase 1α. Journal of Biological Chemistry, 276(21), 17908-17913. https://doi.org/10.1074/jbc.M009677200