MKP-3 Has Essential Roles as a Negative Regulator of the Ras/Mitogen-Activated Protein Kinase Pathway during Drosophila Development

Myungjin Kim, Guang Ho Cha, Sunhong Kim, Jun Hee Lee, Jeehye Park, Hyongjong Koh, Kang-Yell Choi, Jongkyeong Chung

Research output: Contribution to journalArticle

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Abstract

Mitogen-activated protein kinase (MAPK) phosphatase 3 (MKP-3) is a well-known negative regulator in the Ras/extracellular signal-regulated kinase (ERK)-MAPK signaling pathway responsible for cell fate determination and proliferation during development. However, the physiological roles of MKP-3 and the mechanism by which MKP-3 regulates Ras/Drosophila ERK (DERK) signaling in vivo have not been determined. Here, we demonstrated that Drosophila MKP-3 (DMKP-3) is critically involved in cell differentiation, proliferation, and gene expression by suppressing the Ras/DERK pathway, specifically binding to DERK via the N-terminal ERK-binding domain of DMKP-3. Overexpression of DMKP-3 reduced the number of photoreceptor cells and inhibited wing vein differentiation. Conversely, DMKP-3 hypomorphic mutants exhibited extra photoreceptor cells and wing veins, and its null mutants showed striking phenotypes, such as embryonic lethality and severe defects in oogenesis. All of these phenotypes were highly similar to those of the gain-of-function mutants of DERK/rl. The functional interaction between DMKP-3 and the Ras/DERK pathway was further confirmed by genetic interactions between DMKP-3 loss-of-function mutants or overexpressing transgenic flies and various mutants of the Ras/DERK pathway. Collectively, these data provide the direct evidences that DMKP-3 is indispensable to the regulation of DERK signaling activity during Drosophila development.

Original languageEnglish
Pages (from-to)573-583
Number of pages11
JournalMolecular and Cellular Biology
Volume24
Issue number2
DOIs
Publication statusPublished - 2004 Jan 1

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Dual Specificity Phosphatase 1
Mitogen-Activated Protein Kinases
Drosophila
MAP Kinase Signaling System
Extracellular Signal-Regulated MAP Kinases
Photoreceptor Cells
Dual Specificity Phosphatase 6
Veins
Phenotype
Oogenesis
Diptera
Drosophila Mkp3 protein
Cell Differentiation
Cell Proliferation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Kim, Myungjin ; Cha, Guang Ho ; Kim, Sunhong ; Lee, Jun Hee ; Park, Jeehye ; Koh, Hyongjong ; Choi, Kang-Yell ; Chung, Jongkyeong. / MKP-3 Has Essential Roles as a Negative Regulator of the Ras/Mitogen-Activated Protein Kinase Pathway during Drosophila Development. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 2. pp. 573-583.
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MKP-3 Has Essential Roles as a Negative Regulator of the Ras/Mitogen-Activated Protein Kinase Pathway during Drosophila Development. / Kim, Myungjin; Cha, Guang Ho; Kim, Sunhong; Lee, Jun Hee; Park, Jeehye; Koh, Hyongjong; Choi, Kang-Yell; Chung, Jongkyeong.

In: Molecular and Cellular Biology, Vol. 24, No. 2, 01.01.2004, p. 573-583.

Research output: Contribution to journalArticle

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