ArticleThe EMBO journal2002
Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 226 citations in OpenAlex.
- Structural and functional characterisation of ATF2 nuclear import reveals paralogue-selective importin-α recognition and a non-canonical NLS formed in trans.Life science alliance · 2026Article
- Stimulus-Dependent Expression ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.Molecular oncology · 2024Article
- Emerging roles of activating transcription factor 2 in the development of breast cancer: a comprehensive review.Precision clinical medicine · 2023Review
- Isoform-specific optical activation of kinase function reveals p38-ERK signaling crosstalk.RSC chemical biology · 2023Article
- Spatially differential regulation of ATF2 phosphorylation contributes to warning coloration of gregarious locusts.Science advances · 2023Article
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- Resolving the role of podoplanin in the motility of papillary thyroid carcinoma-derived cells using RNA sequencing.Computational and structural biotechnology journal · 2023Article
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- The role of PAF in immunopathology: From immediate hypersensitivity reactions to fungal defense.BioFactors (Oxford, England) · 2022Review
- Injury-induced MAPK activation triggers body axis formation inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Phospho-proteomics identifies a critical role of ATF2 in pseudorabies virus replication.Virologica Sinica · 2022Article
- Golgi Complex: A Signaling Hub in Cancer.Cells · 2022Review
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- Downregulation of KIF15 inhibits the tumorigenesis of non-small-cell lung cancer via inactivating Raf/MEK/ERK signaling.Histology and histopathology · 2022Article
- Combined Quantitative (Phospho)proteomics and Mass Spectrometry Imaging Reveal Temporal and Spatial Protein Changes in Human Intestinal Ischemia-Reperfusion.Journal of proteome research · 2022Article
- Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Review
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- A Novel Small Peptide H-KI20 Inhibits Retinal Neovascularization Through the JNK/ATF2 Signaling Pathway.Investigative ophthalmology & visual science · 2021Article
- NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma.Pharmaceuticals (Basel, Switzerland) · 2020Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription factor ATF2 regulates gene expression in response to environmental changes. Upon exposure to cellular stresses, the mitogen-activated proteinkinase (MAPK) cascades including SAPK/JNK and p38 can enhance ATF2's transactivating function through phosphorylation of Thr69 and Thr71. How ever, the mechanism of ATF2 activation by growth factors that are poor activators of JNK and p38 is still elusive. Here, we show that in fibroblasts, insulin, epidermal growth factor (EGF) and serum activate ATF2 via a so far unknown two-step mechanism involving two distinct Ras effector pathways: the Raf-MEK-ERK pathway induces phosphorylation of ATF2 Thr71, whereas subsequent ATF2 Thr69 phosphorylation requires the Ral-RalGDS-Src-p38 pathway. Cooperation between ERK and p38 was found to be essential for ATF2 activation by these mitogens; the activity of p38 and JNK/SAPK in growth factor-stimulated fibroblasts is insufficient to phosphorylate ATF2 Thr71 or Thr69 + 71 significantly by themselves, while ERK cannot dual phosphorylate ATF2 Thr69 + 71 efficiently. These results reveal a so far unknown mechanism by which distinct MAPK pathways and Ras effector pathways cooperate to activate a transcription factor.
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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.