ArticleMolecular cell2013
MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- FSTL-1 as a Novel Cardiokine of Cardiac Angiogenesis: A Systematic Review.Vascular health and risk management · 2025Pooled it
- A computational rule-based model of MAPK/ERK system regulation.Scientific reports · 2026Article
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- SRC inhibition enables formation of a growth suppressive MAGI1-PP2A complex in isocitrate dehydrogenase-mutant cholangiocarcinoma.Science translational medicine · 2024Article
- Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation.Science signaling · 2024Article
- BRAFScience advances · 2023Article
- Dual role of PID1 in regulating apoptosis induced by distinct anticancer-agents through AKT/Raf-1-dependent pathway in hepatocellular carcinoma.Cell death discovery · 2023Article
- Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.Cancer communications (London, England) · 2023Review
- RETRACTED: The Synergistic Hepatoprotective Activity of Rosemary Essential Oil and Curcumin: The Role of the MEK/ERK Pathway.Molecules (Basel, Switzerland) · 2022Article
- Autocrine FGF1 signaling promotes glucose uptake in adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- MAP2K2 Delays Recovery in Murine Models of Acute Lung Injury and Associates with Acute Respiratory Distress Syndrome Outcome.American journal of respiratory cell and molecular biology · 2022Article
- Review
- Context-Dependent Immunomodulatory Effects of MEK Inhibition Are Enhanced with T-cell Agonist Therapy.Cancer immunology research · 2021Article
- Review
- Review
- MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis.Scientific reports · 2021Article
- Direct stimulation of ERBB2 highlights a novel cytostatic signaling pathway driven by the receptor ThrScientific reports · 2020Article
- CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy.Molecular oncology · 2020Article
- Anti-angiogenic effects of the blue-green alga Arthrospira platensis on pancreatic cancer.Journal of cellular and molecular medicine · 2020Article
- Both Hypoxia-Inducible Factor 1 and MAPK Signaling Pathway Attenuate PI3K/AKT via Suppression of Reactive Oxygen Species in Human Pluripotent Stem Cells.Frontiers in cell and developmental biology · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Raf/MEK/ERK and PI3K/Akt pathways are prominent effectors of oncogenic Ras. These pathways negatively regulate each other, but the mechanism involved is incompletely understood. We now identify MEK1 as an essential regulator of lipid/protein phosphatase PTEN, through which it controls phosphatidylinositol-3-phosphate accumulation and AKT signaling. MEK1 ablation stabilizes AKT activation and, in vivo, causes a lupus-like autoimmune disease and myeloproliferation. Mechanistically, MEK1 is necessary for PTEN membrane recruitment as part of a ternary complex containing the multidomain adaptor MAGI1. Complex formation is independent of MEK1 kinase activity but requires phosphorylation of T292 on MEK1 by activated ERK. Thus, inhibiting the ERK pathway reduces PTEN membrane recruitment, increasing phosphatidylinositol-3-phosphate accumulation and AKT activation. Our data offer a conceptual framework for the observation that activation of the PI3K pathway frequently mediate resistance to MEK inhibitors and for the promising results obtained by combined MEK/PI3K inhibition in preclinical cancer models.
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Registered trials
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.