ArticleScientific reports2017
Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- A critical role of FAK signaling in Rac1-driven melanoma cell resistance to MAPK pathway inhibition.Oncogene · 2025Article
- Phosphorylation of PP2Ac by PKC is a key regulatory step in the PP2A-switch-dependent AKT dephosphorylation that leads to apoptosis.Cell communication and signaling : CCS · 2024Article
- Cell cycle control by the insulin-like growth factor signal: at the crossroad between cell growth and mitotic regulation.Cell cycle (Georgetown, Tex.) · 2023Review
- GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch.Cell communication and signaling : CCS · 2022Article
- Article
- Reserpine improves Enterobacteriaceae resistance in chicken intestine via neuro-immunometabolic signaling and MEK1/2 activation.Communications biology · 2021Article
- Context-Dependent Immunomodulatory Effects of MEK Inhibition Are Enhanced with T-cell Agonist Therapy.Cancer immunology research · 2021Article
- Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders.Journal of medicinal chemistry · 2020Article
- FOXO transcription factor family in cancer and metastasis.Cancer metastasis reviews · 2020Review
- IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas.Signal transduction and targeted therapy · 2020Article
- Review
- PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer.Nature immunology · 2020Article
- FOXO1 and hsa-microRNA-204-5p affect the biologic behavior of MDA-MB-231 breast cancer cells.International journal of clinical and experimental pathology · 2020Article
- Quantitative In Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks.Cell reports · 2019Article
- Inactivation of FOXO1 induces T follicular cell polarization and involves angioimmunoblastic T cell lymphoma.Cancer biology & medicine · 2019Article
- Nuclear ERK: Mechanism of Translocation, Substrates, and Role in Cancer.International journal of molecular sciences · 2019Review
- Phosphorylated Progesterone Receptor Isoforms Mediate Opposing Stem Cell and Proliferative Breast Cancer Cell Fates.Endocrinology · 2019Article
- Intrinsically active MEK variants are differentially regulated by proteinases and phosphatases.Scientific reports · 2018Article
- FoxO transcription factors in cancer metabolism.Seminars in cancer biology · 2018Review
- Goserelin promotes the apoptosis of epithelial ovarian cancer cells by upregulating forkhead box O1 through the PI3K/AKT signaling pathway.Oncology reports · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crosstalk between the ERK cascade and other signaling pathways is one of the means by which it acquires its signaling specificity. Here we identified a direct interaction of both MEK1 and MEK2 with AKT. The interaction is mediated by the proline rich domain of MEK1/2 and regulated by phosphorylation of Ser298 in MEK1, or Ser306 in MEK2, which we identified here as a novel regulatory site. We further developed a blocking peptide, which inhibits the interaction between MEK and AKT, and when applied to cells, affects migration and adhesion, but not proliferation. The specific mechanism of action of the MEK-AKT complex involves phosphorylation of the migration-related transcription factor FoxO1. Importantly, prevention of the interaction results in a decreased metastasis formation in a breast cancer mouse model. Thus, the identified interaction both sheds light on how signaling specificity is determined, and represents a possible new therapeutic target for metastatic cancer.
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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.