ArticleExperimental cell research2015
The MAPK ERK5, but not ERK1/2, inhibits the progression of monocytic phenotype to the functioning macrophage.
Article in Experimental cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- A multi-level exploration of the genetic basis between lung cancer and schizophrenia.Annals of general psychiatry · 2025Article
- Genome-wide screen inbioRxiv : the preprint server for biology · 2025Article
- Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.Biomolecules · 2021Review
- Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis.Cancer research · 2020Article
- Review
- MEK5/ERK5 activation regulates colon cancer stem-like cell properties.Cell death discovery · 2019Article
- Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Nuclear ERK5 inhibits progression of leukemic monocytes to macrophages by regulating the transcription factor PU.1 and heat shock protein HSP70.Leukemia & lymphoma · 2017Article
- Prodifferentiation Activity of Novel Vitamin D₂ Analogs PRI-1916 and PRI-1917 and Their Combinations with a Plant Polyphenol in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2016Article
- Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5.Oncotarget · 2015Article
- Up-regulation of A20/ABIN1 contributes to inefficient M1 macrophage polarization during Hepatitis C virus infection.Virology journal · 2015Article
- Targeting RTK Signaling Pathways in Cancer.Cancers · 2015Review
- The Potential of Vitamin D-Regulated Intracellular Signaling Pathways as Targets for Myeloid Leukemia Therapy.Journal of clinical medicine · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Intracellular signaling pathways present targets for pharmacological agents with potential for treatment of neoplastic diseases, with some disease remissions already recorded. However, cellular compensatory mechanisms usually negate the initial success. For instance, attempts to interrupt aberrant signaling downstream of the frequently mutated ras by inhibiting ERK1/2 has shown only limited usefulness for cancer therapy. Here, we examined how ERK5, that overlaps the functions of ERK1/2 in cell proliferation and survival, functions in a manner distinct from ERK1/2 in human AML cells induced to differentiate by 1,25D-dihydroxyvitamin D3 (1,25D). Using inhibitors of ERK1/2 and of MEK5/ERK5 at concentrations specific for each kinase in HL60 and U937 cells, we observed that selective inhibition of the kinase activity of ERK5, but not of ERK1/2, in the presence of 1,25D resulted in macrophage-like cell morphology and enhancement of phagocytic activity. Importantly, this was associated with increased expression of the macrophage colony stimulating factor receptor (M-CSFR), but was not seen when M-CSFR expression was knocked down. Interestingly, inhibition of ERK1/2 led to activation of ERK5 in these cells. Our results support the hypothesis that ERK5 negatively regulates the expression of M-CSFR, and thus has a restraining function on macrophage differentiation. The addition of pharmacological inhibitors of ERK5 may influence trials of differentiation therapy of AML.
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