ArticleMolecular and cellular biology2004
Mnk2 and Mnk1 are essential for constitutive and inducible phosphorylation of eukaryotic initiation factor 4E but not for cell growth or 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 275 papers, 1 of them a synthesis that pooled it.
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Who cites it
275 citing papers in PubMed, 1 synthesis or guideline pooled it, 495 citations in OpenAlex.
- Adaptation of the Porcine Pituitary Transcriptome, Spliceosome and Editome during Early Pregnancy.International journal of molecular sciences · 2023Pooled it
- Transcriptome-wide splicing analysis reveals HuR-regulated post-transcriptional programs in osteocytes.iScience · 2026Article
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Article
- Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome.Molecular psychiatry · 2026Article
- Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse.Development & reproduction · 2026Review
- The many ways to inhibit translation by Sorafenib in liver cancer cells.Molecular and cellular biochemistry · 2026Article
- Lack of phospho-eIF4E worsens experimental colitis by inhibiting Treg suppressive activity.Journal of inflammation (London, England) · 2025Article
- Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.ACS pharmacology & translational science · 2025Review
- Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer.ACS pharmacology & translational science · 2025Review
- Sortase-Mediated Fluorescent Labeling of eIF4E for Investigating Translation Initiation Mechanisms.Biochemistry · 2025Article
- eIF4F-mediated dysregulation of mRNA translation in cancer.RNA (New York, N.Y.) · 2025Review
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- MNK: A Novel Promising Target for Cancer Immunotherapy.Current medicinal chemistry · 2025Review
- Design, synthesis and biological evaluation of MNK-PROTACs.Molecular diversity · 2024Article
- Article
- PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation.Life science alliance · 2024Article
- The crosstalk between metabolism and translation.Cell metabolism · 2024Review
- Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.Brain : a journal of neurology · 2024Article
- MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.The Journal of clinical investigation · 2024Article
215 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mnk1 and Mnk2 are protein kinases that are directly phosphorylated and activated by extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein (MAP) kinases and implicated in the regulation of protein synthesis through their phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) at Ser209. To investigate their physiological functions, we generated mice lacking the Mnk1 or Mnk2 gene or both; the resulting KO mice were viable, fertile, and developed normally. In embryonic fibroblasts prepared from Mnk1-Mnk2 DKO mice, eIF4E was not detectably phosphorylated at Ser209, even when the ERK and/or p38 MAP kinases were activated. Analysis of embryonic fibroblasts from single KO mice revealed that Mnk1 is responsible for the inducible phosphorylation of eIF4E in response to MAP kinase activation, whereas Mnk2 mainly contributes to eIF4E's basal, constitutive phosphorylation. Lipopolysaccharide (LPS)- or insulin-induced upregulation of eIF4E phosphorylation in the spleen, liver, or skeletal muscle was abolished in Mnk1(-/-) mice, whereas the basal eIF4E phosphorylation levels were decreased in Mnk2(-/-) mice. In Mnk1-Mnk2 DKO mice, no phosphorylated eIF4E was detected in any tissue studied, even after LPS or insulin injection. However, neither general protein synthesis nor cap-dependent translation, as assayed by a bicistronic reporter assay system, was affected in Mnk-deficient embryonic fibroblasts, despite the absence of phosphorylated eIF4E. Thus, Mnk1 and Mnk2 are exclusive eIF4E kinases both in cultured fibroblasts and adult tissues, and they regulate inducible and constitutive eIF4E phosphorylation, respectively. These results strongly suggest that eIF4E phosphorylation at Ser209 is not essential for cell growth during development.
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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.