ArticleNature communications2020
Phosphoproteomics identifies a bimodal EPHA2 receptor switch that promotes embryonic stem cell differentiation.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Phosphorylation enables progressive microtubule-associated protein proteolysis and functionalisation during neural development.bioRxiv : the preprint server for biology · 2025Article
- EPHA2 is a novel cell surface marker of OCT4-positive undifferentiated cells during the differentiation of mouse and human pluripotent stem cells.Stem cells translational medicine · 2024Article
- Hypoxia-induced TGFBI maintains glioma stem cells by stabilizing EphA2.Theranostics · 2024Article
- ERK1/2-RSK regulation of oestrogen homeostasis.The FEBS journal · 2023Review
- Tandem Mass Tagging-Based Quantitative Proteomics Analysis Reveals Damage to the Liver and Brain ofAntioxidants (Basel, Switzerland) · 2022Article
- Regulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker.Nature communications · 2021Article
- A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development.PLoS computational biology · 2021Article
- EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?Cancers · 2021Review
- PGE2 Supplementation of Oocyte Culture Media Improves the Developmental and Cryotolerance Performance of Bovine Blastocysts Derived From a Serum-FreeFrontiers in cell and developmental biology · 2021Article
- Eph-Ephrin Signaling Mediates Cross-Talk Within the Bone Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Harnessing the Power of Eph/ephrin Biosemiotics for Theranostic Applications.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Embryonic Stem Cell (ESC) differentiation requires complex cell signalling network dynamics, although the key molecular events remain poorly understood. Here, we use phosphoproteomics to identify an FGF4-mediated phosphorylation switch centred upon the key Ephrin receptor EPHA2 in differentiating ESCs. We show that EPHA2 maintains pluripotency and restrains commitment by antagonising ERK1/2 signalling. Upon ESC differentiation, FGF4 utilises a bimodal strategy to disable EPHA2, which is accompanied by transcriptional induction of EFN ligands. Mechanistically, FGF4-ERK1/2-RSK signalling inhibits EPHA2 via Ser/Thr phosphorylation, whilst FGF4-ERK1/2 disrupts a core pluripotency transcriptional circuit required for Epha2 gene expression. This system also operates in mouse and human embryos, where EPHA receptors are enriched in pluripotent cells whilst surrounding lineage-specified trophectoderm expresses EFNA ligands. Our data provide insight into function and regulation of EPH-EFN signalling in ESCs, and suggest that segregated EPH-EFN expression coordinates cell fate with compartmentalisation during early embryonic development.
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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.