ArticlePloS one2015
Phosphorylation of ERK5 on Thr732 is associated with ERK5 nuclear localization and ERK5-dependent transcription.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- MicroRNAs as diagnostic biomarkers in diabetes male infertility: a systematic review.Molecular biology reports · 2024Pooled it
- Targeting the Extracellular Signal-Regulated Kinase 5-Cellular Jun-Vimentin Axis to Inhibit Epithelial-Mesenchymal Transition and Metastasis in Patients with Triple-Negative Breast Cancer.International journal of medical sciences · 2026Article
- scTIGER: A Deep-Learning Method for Inferring Gene Regulatory Networks from Case versus Control scRNA-seq Datasets.International journal of molecular sciences · 2023Article
- Newt A1 cell-derived extracellular vesicles promote mammalian nerve growth.Scientific reports · 2023Article
- Review
- Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy.Journal of medicinal chemistry · 2023Review
- Article
- Review
- ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled?Frontiers in cell and developmental biology · 2022Review
- A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2.International microbiology : the official journal of the Spanish Society for Microbiology · 2021Review
- MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes.Molecular medicine (Cambridge, Mass.) · 2021Article
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- Diverse and converging roles of ERK1/2 and ERK5 pathways on mesenchymal to epithelial transition in breast cancer.Translational oncology · 2021Article
- MicroRNA-211 Modulates the DUSP6-ERK5 Signaling Axis to Promote BRAFThe Journal of investigative dermatology · 2021Article
- Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.Biomolecules · 2021Review
- Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for….Biochemical Society transactions · 2020Review
- Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy.International journal of molecular sciences · 2020Review
- Discovery of a Gatekeeper Residue in the C-Terminal Tail of the Extracellular Signal-Regulated Protein Kinase 5 (ERK5).International journal of molecular sciences · 2020Article
- Targeting the Extracellular Signal-Regulated Kinase 5 Pathway to Suppress Human Chronic Myeloid Leukemia Stem Cells.Stem cell reports · 2018Article
- ERK5 Phosphorylates KInternational journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular signal-regulated kinases (ERKs) play critical roles in numerous cellular processes, including proliferation and differentiation. ERK5 contains a kinase domain at the N-terminal, and the unique extended C-terminal includes multiple autophosphorylation sites that enhance ERK5-dependent transcription. However, the impact of phosphorylation at the various sites remain unclear. In this study, we examined the role of phosphorylation at the ERK5 C-terminal. We found that a constitutively active MEK5 mutant phosphorylated ERK5 at the TEY motif, resulting in the sequential autophosphorylation of multiple C-terminal residues, including Thr732 and Ser769/773/775. However, when ERK1/2 was selectively activated by an oncogenic RAS mutant, ERK5 phosphorylation at Thr732 was induced without affecting the phosphorylation status at TEY or Ser769/773/775. The Thr732 phosphorylation was U0126-sensitive and was observed in a kinase-dead mutant of ERK5 as well, suggesting that ERK1/2 can phosphorylate ERK5 at Thr732. This phosphorylation was also promoted by epidermal growth factor and nerve growth factor in HEK293 and PC12 cells, respectively. The ERK5-T732A mutant was localized in the cytosol under basal conditions. In contrast, ERK5 phosphorylated at Thr732 via the RAS-ERK1/2 pathway and ERK5-T732E, which mimics the phosphorylated form, were localized in both the nucleus and cytosol. Finally, ER-32A and U0126 blocked ERK5-dependent MEF2C transcriptional activity. Based on these findings, we propose a novel cross-talk mechanism in which ERK1/2, following activation by growth factor stimulation, phosphorylates ERK5 at Thr732. This phosphorylation event is responsible for ERK5 nuclear localization and ERK5-dependent transcription.
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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.