N-myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells

Toko Chida, Masakatsu Ando, Tasuku Matsuki, Yutaro Masu, Yuko Nagaura, Teruko Takano-Yamamoto, Shinri Tamura, Takayasu Kobayashi

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

PPM [metal-dependent protein phosphatase, formerly called PP2C (protein phosphatase 2C)] family members play essential roles in regulating a variety of signalling pathways. While searching for protein phosphatase(s) that act on AMPK (AMP-activated protein kinase), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the α subunit of AMPK (AMPKα) in cells. N-Myristoylation was also required for two other functions of PPM1A and PPM1B in cells. Although a non-myristoylated mutation (G2A) of PPM1A and PPM1B prevented membrane association, this relocalization did not likely cause the decreased activity towards AMPKα. In in vitro experiments, the G2A mutants exhibited reduced activities towards AMPKα, but much higher specific activity against an artificial substrate, PNPP (p-nitrophenyl phosphate), compared with the wild-type counterparts. Taken together, the results of the present study suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.

Original languageEnglish
Pages (from-to)741-749
Number of pages9
JournalBiochemical Journal
Volume449
Issue number3
DOIs
Publication statusPublished - 2013 Feb 1

Keywords

  • AMP-activated protein kinase (AMPK)
  • Metal-dependent protein phosphatase 1A (PPM1A)
  • Metal-dependent protein phosphatase 1B (PPM1B)
  • N-myristoylation
  • Protein phosphatase 2C (PP2C)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'N-myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells'. Together they form a unique fingerprint.

Cite this