ArticleMolecular and cellular biology2004
MKP-3 has essential roles as a negative regulator of the Ras/mitogen-activated protein kinase pathway during Drosophila development.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 42 citations in OpenAlex.
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- Comparative Genomics Sheds Light on the Convergent Evolution of Miniaturized Wasps.Molecular biology and evolution · 2021Article
- A Functional Analysis of theG3 (Bethesda, Md.) · 2020Article
- Genetic regulation and function of epidermal growth factor receptor signalling in patterning of the embryonic Drosophila brain.Open biology · 2016Article
- Src kinase function controls progenitor cell pools during regeneration and tumor onset in the Drosophila intestine.Oncogene · 2015Article
- A systems-level interrogation identifies regulators of Drosophila blood cell number and survival.PLoS genetics · 2015Article
- Engineered single nucleotide polymorphisms in the mosquito MEK docking site alter Plasmodium berghei development in Anopheles gambiae.Parasites & vectors · 2014Article
- Substrate-dependent control of MAPK phosphorylation in vivo.Molecular systems biology · 2011Article
- Mechanisms of regulation of oligodendrocyte development by p38 mitogen-activated protein kinase.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in drosophila gut.Nature immunology · 2009Article
- Nodal points and complexity of Notch-Ras signal integration.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Signaling gradients in cascades of two-state reaction-diffusion systems.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila melanogaster.The Journal of cell biology · 2008Article
- WT1 induction of mitogen-activated protein kinase phosphatase 3 represents a novel mechanism of growth suppression.Molecular cancer research : MCR · 2008Article
- Article
- An intrinsic cell cycle checkpoint pathway mediated by MEK and ERK in Drosophila.Developmental cell · 2006Article
- Inhibition of ERK-MAP kinase signaling by RSK during Drosophila development.The EMBO journal · 2006Article
- Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation.Molecular and cellular biology · 2005Article
- Split ends antagonizes the Notch and potentiates the EGFR signaling pathways during Drosophila eye development.Mechanisms of developmentArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
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.
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