Phosphorylation and activation of the ATP-Mg-dependent protein phosphatase by the mitogen-activated protein kinase

Q. M. Wang, K. L. Guan, P. J. Roach, A. A. DePaoli-Roach

Research output: Contribution to journalArticle

41 Scopus citations


Inhibitor-2 (I-2) is the regulatory subunit of the cytosolic ATP-Mg- dependent form of type 1 serine/threonine protein phosphatase and its phosphorylation at Thr-72 by glycogen synthase kinase-3 results in phosphatase activation. Activation of cytosolic type 1 phosphatase has been observed in cells treated with growth factors. Reported here is the phosphorylation and activation of the ATP-Mg-dependent phosphatase by mitogen-activated protein kinase (MAPK). Recombinant I-2 was phosphorylated by activated MAPK to an extent (~0.3 mol of phosphate/mol of polypeptide) similar to that reported for phosphorylation by the α isoform of glycogen synthase kinase-3. The phosphorylation of I-2 by MAPK was exclusively at Thr- 72, the site involved in the activation of phosphatase. Incubation of MAPK with purified ATP-Mg-dependent phosphatase resulted in phosphorylation of the I-2 component and activation of the phosphatase. Ribosomal S6 protein kinase II (p90(rsk)) was also able to phosphorylate the recombinant I-2; however, this phosphorylation occurred on serines and had no effect on phosphatase activation. Our data may explain growth factor-induced activation of the ATP- Mg-dependent phosphatase and suggest that MAPK may be the physiological kinase responsible for the activation of cytosolic type 1 phosphatase in response to insulin and/or other growth factors.

Original languageEnglish (US)
Pages (from-to)18352-18358
Number of pages7
JournalJournal of Biological Chemistry
Issue number31
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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