Regulation of Drosophila MKP-3 by Drosophila ERK

Sung Eun Kim, Sun Hong Kim, Kang-Yell Choi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

DMKP-3 is a Drosophila dual-specificity phosphatase, which has high substrate specificity for Drosophila extracellular signal-regulated kinases (DERK). By in vitro reconstitution experiments, we found that DERK activates DMKP-3. Moreover, DMKP-3 was specifically activated by the addition of DERK but not by DJNK, Dp38, or Sevenmaker DERK D334N, a DMKP-3-binding mutant. The phosphatase activity of DMKP-3-R56A/R57A, a DERK-binding mutant, was not increased by DERK. Significantly, mammalian MKP-3 was also found to be activated by DERK. This cross-reactivity suggests a high level of conservation of the activation mechanism of ERK-specific phosphatases in Drosophila and mammals. When DMKP-3 was co-expressed with DERK in Drosophila Schneider cells, DMKP-3 protein levels increased, but this was not observed for the co-expressions of DJNK or Dp38. The stabilizations of the DERK binding mutants (DMKP-3-RR and DMKP-3-CA-RR) were not increased by DERK co-expression. Our results suggest that DERK specifically regulates DMKP-3 in terms of its enzyme activity and protein stability, and that direct protein-protein interaction is an essential aspect of this regulation.

Original languageEnglish
Pages (from-to)51-61
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
Publication statusPublished - 2003 Jan 1

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Extracellular Signal-Regulated MAP Kinases
Drosophila
Phosphoric Monoester Hydrolases
Proteins
Drosophila Mkp3 protein
Dual-Specificity Phosphatases
Mammals
Enzyme activity
Enzyme Stability
Protein Stability
Conservation
Substrate Specificity
Stabilization
Chemical activation

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

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abstract = "DMKP-3 is a Drosophila dual-specificity phosphatase, which has high substrate specificity for Drosophila extracellular signal-regulated kinases (DERK). By in vitro reconstitution experiments, we found that DERK activates DMKP-3. Moreover, DMKP-3 was specifically activated by the addition of DERK but not by DJNK, Dp38, or Sevenmaker DERK D334N, a DMKP-3-binding mutant. The phosphatase activity of DMKP-3-R56A/R57A, a DERK-binding mutant, was not increased by DERK. Significantly, mammalian MKP-3 was also found to be activated by DERK. This cross-reactivity suggests a high level of conservation of the activation mechanism of ERK-specific phosphatases in Drosophila and mammals. When DMKP-3 was co-expressed with DERK in Drosophila Schneider cells, DMKP-3 protein levels increased, but this was not observed for the co-expressions of DJNK or Dp38. The stabilizations of the DERK binding mutants (DMKP-3-RR and DMKP-3-CA-RR) were not increased by DERK co-expression. Our results suggest that DERK specifically regulates DMKP-3 in terms of its enzyme activity and protein stability, and that direct protein-protein interaction is an essential aspect of this regulation.",
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Regulation of Drosophila MKP-3 by Drosophila ERK. / Kim, Sung Eun; Kim, Sun Hong; Choi, Kang-Yell.

In: Annals of the New York Academy of Sciences, Vol. 1010, 01.01.2003, p. 51-61.

Research output: Contribution to journalArticle

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