ArticlePloS one2012
Tgf-beta induced Erk phosphorylation of smad linker region regulates smad signaling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.The Journal of allergy and clinical immunology · 2019Pooled it
- Impaired TGFβ Signaling in Plaque-Associated Microglia.Biomolecules · 2026Article
- Ivermectin inhibits ER, HER2, and TGF-β pathways in ER-positive and endocrine-resistant breast cancer cells.PloS one · 2026Article
- Research Progress and Future Directions in Immune Cell Crosstalk in the Esophageal Cancer: A Bibliometric Analysis.Journal of inflammation research · 2026Review
- SMAD2 S-palmitoylation promotes its linker region phosphorylation and TScience signaling · 2025Article
- Dual inhibition of TGFβ and PDGF improves RV remodeling and function in response to RV pressure or volume-loading.Physiological reports · 2025Article
- Role of DDR1 in Regulating MMPs in External Root Resorption.International journal of molecular sciences · 2024Article
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- Differential Smad2/3 linker phosphorylation is a crosstalk mechanism of Rho/ROCK and canonical TGF-β3 signaling in tenogenic differentiation.Scientific reports · 2024Article
- MAP3K19 Affects TWEAK-Induced Response in Cultured Bronchial Epithelial Cells and Regulates Allergic Airway Inflammation in an Asthma Murine Model.Current issues in molecular biology · 2023Article
- State- and stimulus-specific dynamics of SMAD signaling determine fate decisions in individual cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Nedd4L suppression in lung fibroblasts facilitates pathogenesis of lung fibrosis.Translational research : the journal of laboratory and clinical medicine · 2023Article
- MAPKs in the early steps of senescence implemEMTation.Frontiers in cell and developmental biology · 2023Article
- Extracellular matrix stiffness-The central cue for skin fibrosis.Frontiers in molecular biosciences · 2023Review
- TGFβ pathway is required for viable gestation of Fanconi anemia embryos.PLoS genetics · 2022Article
- BMS-202, a PD-1/PD-L1 inhibitor, decelerates the pro-fibrotic effects of fibroblasts derived from scar tissues via ERK and TGFβ1/Smad signaling pathways.Immunity, inflammation and disease · 2022Article
- Endothelin-1 Stimulates PAI-1 Protein Expression via Dual Transactivation Pathway Dependent ROCK and Phosphorylation of Smad2L.Cell journal · 2022Article
- Endothelin-1 dependent expression of GAG genes involves NOX and p38 mediated Smad linker region phosphorylation.Clinical and experimental pharmacology & physiology · 2022Article
- Intervertebral disc degeneration is rescued by TGFβ/BMP signaling modulation in an ex vivo filamin B mouse model.Bone research · 2022Article
- In Vivo Induction of Regulatory T Cells Via CTLA-4 Signaling Peptide to Control Autoimmune Encephalomyelitis and Prevent Disease Relapse.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
16 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
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The Transforming Growth Factor-Beta (TGF-β) family is involved in regulating a variety of cellular processes such as apoptosis, differentiation, and proliferation. TGF-β binding to a Serine/Threonine kinase receptor complex causes the recruitment and subsequent activation of transcription factors known as smad2 and smad3. These proteins subsequently translocate into the nucleus to negatively or positively regulate gene expression. In this study, we define a second signaling pathway leading to TGF-β receptor activation of Extracellular Signal Regulated Kinase (Erk) in a cell-type dependent manner. TGF-β induced Erk activation was found in phenotypically normal mesenchymal cells, but not normal epithelial cells. By activating phosphotidylinositol 3-kinase (PI3K), TGF-β stimulates p21-activated kinase2 (Pak2) to phosphorylate c-Raf, ultimately resulting in Erk activation. Activation of Erk was necessary for TGF-β induced fibroblast replication. In addition, Erk phosphorylated the linker region of nuclear localized smads, resulting in increased half-life of C-terminal phospho-smad 2 and 3 and increased duration of smad target gene transcription. Together, these data show that in mesenchymal cell types the TGF-β/PI3K/Pak2/Raf/MEK/Erk pathway regulates smad signaling, is critical for TGF-β-induced growth and is part of an integrated signaling web containing multiple interacting pathways rather than discrete smad/non-smad pathways.
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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.