Regular Article
Tautomycetin Is a Novel and Specific Inhibitor of Serine/Threonine Protein Phosphatase Type 1, PP1

https://doi.org/10.1006/bbrc.2001.5596Get rights and content

Abstract

Here we isolated tautomycetin, TC, and examined its phosphatase inhibitory activity. Recently we have reported that the left-hand moiety of tautomycin, TM, and the right one containing the spiroketal are essentially required for inhibition of protein phosphatase, PP, and induction of apoptosis, respectively. TC is structurally almost identical to TM except that TC is lacking the spiroketal, which has the potential apoptosis-inducing activity. TC specifically inhibited PP1 activity, IC50 values for purified PP1 and PP2A enzymes being 1.6 and 62 nM, respectively, whereas the IC50 values of TM were 0.21 and 0.94 nM, respectively. These results demonstrate that TC is the most specific PP1 inhibitor out of over 40 species of natural phosphatase inhibitors reported, strongly suggesting that TC is a novel powerful tool to elucidate the physiological roles of PP1 in various biological events.

References (29)

  • T. Hunter

    Cell

    (1995)
  • P.T. Cohen

    Trends Biochem. Sci.

    (1997)
  • A.A. Depaoli-Roach et al.

    Adv. Enzyme. Regul.

    (1994)
  • H. Shima et al.

    Biochem. Biophys. Res. Commun.

    (1993)
  • E. Sontag

    Cell. Signal.

    (2001)
  • B. Favre et al.

    J. Biol. Chem.

    (1997)
  • H. Ishihara et al.

    Biochem. Biophys. Res. Commun.

    (1989)
  • M. Suganuma et al.

    Toxicon

    (1992)
  • T. Kawamura et al.

    Biochem. Pharmacol.

    (1998)
  • J.H. Connor et al.

    J. Biol. Chem.

    (1999)
  • C. MacKintosh et al.

    FEBS Lett.

    (1990)
  • S. Mitsuhashi et al.

    Bioorg. Med. Chem. Lett.

    (1999)
  • M.M. Bradford

    Anal. Biochem.

    (1976)
  • P. Cohen et al.

    Methods Enzymol.

    (1988)
  • Cited by (100)

    • Activation of the kidney sodium chloride cotransporter by the β2-adrenergic receptor agonist salbutamol increases blood pressure

      2021, Kidney International
      Citation Excerpt :

      In the presence of CA, although salbutamol still had a significant effect on the pT58NCC/NCC ratio, the magnitude of change was not as large as in the absence of CA, possibly due to near maximal NCC phosphorylation in the presence of CA. In similar experiments, 50 nmol/l tautomycetin (50% inhibitory concentration values = 1.6 and 62 nmol/l for PP1 and protein phosphatase 2, respectively47) alone did not change the pT58NCC/NCC and pSPAK/SPAK ratios (Figure 7c and d). However, in the presence of tautomycetin, the salbutamol-induced increase in NCC phosphorylation was significantly greater (Figure 7c and d).

    • RSK-MASTL Pathway Delays Meiotic Exit in Mouse Zygotes to Ensure Paternal Chromosome Stability

      2018, Developmental Cell
      Citation Excerpt :

      In order to address the physiological importance of the delay in PNonset, we sought to accelerate PNonset. First, we tested phosphatase involvement in temporal regulation of PNonset by treatment with okadaic acid or tautomycetin, highly selective inhibitors of PP2A-B55 and PP1, respectively (Cohen et al., 1989; Mitsuhashi et al., 2001). The inhibitors were used at a concentration below the level that causes premature chromosome condensation (Dyban et al., 1993) (Figure S1A).

    View all citing articles on Scopus
    1

    To whom correspondence should be addressed. Fax: +81-11-707-6839. E-mail: [email protected].

    View full text