ArticleMolecular and cellular biology2002
Erk5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB2.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82 citing papers in PubMed, 182 citations in OpenAlex.
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- Targeting the MAPK signaling pathway: implications and prospects of flavonoids in 3P medicine as modulators of cancer cell plasticity and therapeutic resistance in breast cancer patients.The EPMA journal · 2025Article
- Peptidylarginine deiminase 3 modulates response to neratinib in HER2 positive breast cancer.Oncogenesis · 2024Article
- ERK5 Interacts with Mitochondrial Glutaminase and Regulates Its Expression.International journal of molecular sciences · 2024Article
- An amino acid transporter subunit as an antibody-drug conjugate target in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications.Experimental & molecular medicine · 2023Article
- Neuregulin modulates hormone receptor levels in breast cancer through concerted action on multiple signaling pathways.Clinical science (London, England : 1979) · 2023Article
- Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation.Cell chemical biology · 2022Article
- The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.Cellular and molecular life sciences : CMLS · 2022Article
- ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.Cancers · 2022Article
- Surfaceome analyses uncover CD98hc as an antibody drug-conjugate target in triple negative breast cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Inhibiting ERK5 overcomes breast cancer resistance to anti-HER2 therapy by targeting the G1/S cell cycle transition.Cancer research communications · 2022Article
- Modelling hypersensitivity to trastuzumab defines biomarkers of response in HER2 positive breast cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Extracellular Signal-Regulated Kinase 5 Regulates the Malignant Phenotype of Cholangiocarcinoma Cells.Hepatology (Baltimore, Md.) · 2021Article
- Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer.NPJ precision oncology · 2021Article
- Article
- PDCD4 limits prooncogenic neuregulin-ErbB signaling.Cellular and molecular life sciences : CMLS · 2021Article
- 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
- Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy.International journal of molecular sciences · 2020Review
- Paclitaxel-Trastuzumab Mixed Nanovehicle to Target HER2-Overexpressing Tumors.Nanomaterials (Basel, Switzerland) · 2019Article
22 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The four receptor tyrosine kinases of the ErbB family play essential roles in several physiological processes and have also been implicated in tumor generation and/or progression. Activation of ErbB1/EGFR is mainly triggered by epidermal growth factor (EGF) and other related ligands, while activation of ErbB2, ErbB3, and ErbB4 receptors occurs by binding to another set of EGF-like ligands termed neuregulins (NRGs). Here we show that the Erk5 mitogen-activated protein kinase (MAPK) pathway participates in NRG signal transduction. In MCF7 cells, NRG activated Erk5 in a time- and dose-dependent fashion. The action of NRG on Erk5 was dependent on the kinase activity of ErbB receptors but was independent of Ras. Expression in MCF7 cells of a dominant negative form of Erk5 resulted in a significant decrease in NRG-induced proliferation of MCF7 cells. Analysis of Erk5 in several human tumor cell lines indicated that a constitutively active form of this kinase was present in the BT474 and SKBR3 cell lines, which also expressed activated forms of ErbB2, ErbB3, and ErbB4. Treatments aimed at decreasing the activity of these receptors caused Erk5 inactivation, indicating that the active form of Erk5 present in BT474 and SKBR3 cells was due to a persistent positive stimulus originating at the ErbB receptors. In BT474 cells expression of the dominant negative form of Erk5 resulted in reduced proliferation, indicating that in these cells Erk5 was also involved in the control of proliferation. Taken together, these results suggest that Erk5 may play a role in the regulation of cell proliferation by NRG receptors and indicate that constitutively active NRG receptors may induce proliferative responses in cancer cells through this MAPK pathway.
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