ArticleMolecular and cellular biology2005
Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 134 citations in OpenAlex.
- DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Journal of biomedical science · 2026Review
- Breaking the ERK1/2 negative feedback loop: avoiding reactivation and acquisition of resistance by ERK1/2 to anti-cancer agents.Frontiers in oncology · 2026Review
- Arthritogenicity of CD11b + Gr1 + myeloid cells is dependent on dual specificity phosphatase 6 (DUSP6).Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- DUSP6 is upregulated in metastasis and influences migration and metabolism in pancreatic cancer cells.Scientific reports · 2025Article
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response.Development (Cambridge, England) · 2024Article
- Article
- DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.Purinergic signalling · 2024Article
- Acute Endoplasmic Reticulum Stress Suppresses Hepatic Gluconeogenesis by Stimulating MAPK Phosphatase 3 Degradation.International journal of molecular sciences · 2023Article
- Upregulation of the EGFR/MEK1/MAPK1/2 signaling axis as a mechanism of resistance to antiestrogen‑induced BimEL dependent apoptosis in ERInternational journal of oncology · 2023Article
- Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes.Nature communications · 2022Article
- Biphasic Regulation of Mitogen-Activated Protein Kinase Phosphatase 3 in Hypoxic Colon Cancer Cells.Molecules and cells · 2021Article
- Dual-specificity phosphatase (DUSP6) in human glioblastoma: epithelial-to-mesenchymal transition (EMT) involvement.BMC research notes · 2020Article
- Regulation of ERK basal and pulsatile activity control proliferation and exit from the stem cell compartment in mammalian epidermis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Angiotensin II-upregulated MAP kinase phosphatase-3 modulates FOXO1 and p21 in adrenocortical H295R cells.Heliyon · 2020Article
- DUSP6 SUMOylation protects cells from oxidative damage via direct regulation of Drp1 dephosphorylation.Science advances · 2020Article
- Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability.International journal of molecular sciences · 2019Review
- Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells.International journal of molecular sciences · 2019Review
- Article
- Dual-specificity phosphatase 6 (DUSP6): a review of its molecular characteristics and clinical relevance in cancer.Cancer biology & medicine · 2018Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen-activated protein (MAP) kinase phosphatases (MKPs) are dual-specificity phosphatases that dephosphorylate phosphothreonine and phosphotyrosine residues within MAP kinases. Here, we describe a novel posttranslational mechanism for regulating MKP-3/Pyst1/DUSP6, a member of the MKP family that is highly specific for extracellular signal-regulated kinase 1 and 2 (ERK1/2) inactivation. Using a fibroblast model in which the expression of either MKP-3 or a more stable MKP-3-green fluorescent protein (GFP) chimera was induced by tetracycline, we found that serum induces the phosphorylation of MKP-3 and its subsequent degradation by the proteasome in a MEK1 and MEK2 (MEK1/2)-ERK1/2-dependent manner. In vitro phosphorylation assays using glutathione S-transferase (GST)-MKP-3 fusion proteins indicated that ERK2 could phosphorylate MKP-3 on serines 159 and 197. Tetracycline-inducible cell clones expressing either single or double serine mutants of MKP-3 or MKP-3-GFP confirmed that these two sites are targeted by the MEK1/2-ERK1/2 module in vivo. Double serine mutants of MKP-3 or MKP-3-GFP were more efficiently protected from degradation than single mutants or wild-type MKP-3, indicating that phosphorylation of either serine by ERK1/2 enhances proteasomal degradation of MKP-3. Hence, double mutation caused a threefold increase in the half-life of MKP-3. Finally, we show that the phosphorylation of MKP-3 has no effect on its catalytic activity. Thus, ERK1/2 exert a positive feedback loop on their own activity by promoting the degradation of MKP-3, one of their major inactivators in the cytosol, a situation opposite to that described for the nuclear phosphatase MKP-1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.