ArticleNature structural & molecular biology2012
ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4.
Article in Nature structural & molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells.Stem cell research & therapy · 2022Pooled it
- The skin-specific long non-coding RNA TEDAR orchestrates late epidermal differentiation via an ERK-KLF4 cytoplasmic regulatory axis.Cell death & disease · 2026Article
- ERK phosphorylates HNRNPF to promote the proliferation and suppress the differentiation of embryonic stem cells.Nucleic acids research · 2026Article
- Dynamic phosphorylation of DGCR8 regulates embryonic stem cell differentiation and microprocessor function.Frontiers in cell and developmental biology · 2026Article
- Selectively Inhibition of MAPK pathway showed positive effects on Porcine embryo-derived stem cells pluripotency.Scientific reports · 2025Article
- Cell state dynamics during early stages of serous endometrial carcinoma.The Journal of pathology · 2025Article
- PP2Acα Deficiency in Vascular Smooth Muscle Cells Accelerates Aortic Aneurysm and Dissection by Regulating KLF4 Phosphorylation and Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- KLF4 enhances transplantation-induced hematopoiesis by inhibiting TLRs and noncanonical NFκB signaling at a steady state.Experimental hematology · 2025Article
- ERK phosphorylates ESRRB to regulate the self-renewal and differentiation of mouse embryonic stem cells.Stem cell reports · 2025Article
- The reprogramming factor KLF4 in normal and malignant blood cells.Frontiers in immunology · 2025Review
- Mitotic Kinases Aurora-A, Plk1, and Cdk1 Interact with Elk-1 Transcription Factor through the N-Terminal Domain.International journal of cell biology · 2024Article
- Early Postnatal Expression of Tgfβ-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH.Stem cells translational medicine · 2023Article
- Modeling unveils sex differences of signaling networks in mouse embryonic stem cells.Molecular systems biology · 2023Article
- Biphasic JNK-Erk signaling separates the induction and maintenance of cell senescence after DNA damage induced by topoisomerase II inhibition.Cell systems · 2023Article
- Embryonic stem cell ERK, AKT, plus STAT3 response dynamics combinatorics are heterogeneous but NANOG state independent.Stem cell reports · 2023Article
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- Review
- Maternal Undernutrition Induces Cell Signalling and Metabolic Dysfunction in Undifferentiated Mouse Embryonic Stem Cells.Stem cell reviews and reports · 2023Article
42 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
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding and controlling the mechanism by which stem cells balance self-renewal versus differentiation is of great importance for stem cell therapeutics. Klf4 promotes the self-renewal of embryonic stem cells, but the precise mechanism regulating this role of Klf4 is unclear. We found that ERK1 or ERK2 binds the activation domain of Klf4 and directly phosphorylates Klf4 at Ser123. This phosphorylation suppresses Klf4 activity, inducing embryonic stem cell differentiation. Conversely, inhibition of Klf4 phosphorylation enhances Klf4 activity and suppresses embryonic stem cell differentiation. Notably, phosphorylation of Klf4 by ERKs causes recruitment and binding of the F-box proteins βTrCP1 or βTrCP2 (components of an ubiquitin E3 ligase) to the Klf4 N-terminal domain, which results in Klf4 ubiquitination and degradation. Overall, our data provide a molecular basis for the role of ERK1 and ERK2 in regulating Klf4-mediated mouse embryonic stem cell self-renewal.
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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.