Phoslactomycin targets cysteine-269 of the protein phosphatase 2A catalytic subunit in cells

Takayuki Teruya, Siro Simizu, Naoki Kanoh, Hiroyuki Osada

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


According to the chemical genetic approach, small molecules that bind directly to proteins are used to analyze protein function, thereby enabling the elucidation of complex mechanisms in mammal cells. Thus, it is very important to identify the molecular targets of compounds that induce a unique phenotype in a target cell. Phoslactomycin A (PLMA) is known to be a potent inhibitor of protein Ser/Thr phosphatase 2A (PP2A); however, the inhibitory mechanism of PP2A by PLMA has not yet been elucidated. Here, we demonstrated that PLMA directly binds to the PP2A catalytic subunit (PP2Ac) in cells by using biotinylated PLMA, and the PLMA-binding site was identified as the Cys-269 residue of PP2Ac. Moreover, we revealed that the Cys-269 contributes to the potent inhibition of PP2Ac activity by PLMA. These results suggest that PLMA is a PP2A-selective inhibitor and is therefore expected to be useful for future investigation of PP2A function in cells.

Original languageEnglish
Pages (from-to)2463-2468
Number of pages6
JournalFEBS Letters
Issue number11
Publication statusPublished - 2005 Apr 25
Externally publishedYes


  • Chemical genetics
  • Phoslactomycin
  • Phosphatase
  • Protein serine/threonine phosphatase 2A

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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