ArticleFrontiers in cell and developmental biology2019
Fibroblast Growth Factor 2 Protein Stability Provides Decreased Dependence on Heparin for Induction of FGFR Signaling and Alters ERK Signaling Dynamics.
Article in Frontiers in cell and developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Fibroblast growth factors in ischemic stroke: Therapeutic potential and clinical challenges.Acta pharmacologica Sinica · 2026Review
- Synthetic Heparan Sulfate-like Oligosaccharides as Tools to Decipher Growth Factor Recognition.Journal of medicinal chemistry · 2026Article
- Phased affinity-controlled delivery of vascular endothelial growth factor, fibroblast growth factor-2, and platelet derived growth factor enhances in vitro angiogenesis.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Towards Cost-Effective and Sustainable Media Formulations for Terrestrial and Aquatic Cellular Agriculture.Foods (Basel, Switzerland) · 2026Review
- Structure-function relationship in FGF signaling: rational design of highly stable FGF2 variants and their effect on cell growth, metabolism, and survival.Journal of biological engineering · 2026Article
- Probenecid-Mediated Pannexin-1 Inhibition Preserves βFGF-Driven Regenerative Responses in Human Dermal Fibroblasts.International journal of molecular sciences · 2026Article
- bFGF Oligomeric Stability Drives Functional Performance in Human Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
- Environmental enrichment and physical exercise prevent stress-induced social avoidance and blood-brain barrier alterations via Fgf2.Nature communications · 2026Article
- Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.Current pharmaceutical design · 2026Review
- Developing FGF2 Mutants with Selectively Reduced Heparan Sulfate Affinity to Explore their Impact on FGFR1 Signaling.Chembiochem : a European journal of chemical biology · 2025Article
- Cloning, expression and functional characterization of prepared bovine, salmon, and cod basic fibroblast growth factor-2.NPJ science of food · 2025Article
- Preadipocyte Uncoupling Protein 1 Expression Invoked by Fibroblast Growth Factors Imprints on Post-Differentiation White and Brown Adipocyte Phenotype.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Low-cost food-grade alternatives for serum albumins in FBS-free cell culture media.Scientific reports · 2025Article
- LRO biogenesis and function: what can we learn from mast cells?Frontiers in cell and developmental biology · 2025Review
- Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB.Journal of structural biology: X · 2024Article
- The Immobilization of an FGF2-Derived Peptide on Culture Plates Improves the Production and Therapeutic Potential of Extracellular Vesicles from Wharton's Jelly Mesenchymal Stem Cells.International journal of molecular sciences · 2024Article
- In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Fibroblast-induced mammary epithelial branching depends on fibroblast contractility.PLoS biology · 2024Article
- Enhancement of hMSC In Vitro Proliferation by Surface Immobilization of a Heparin-Binding Peptide.Molecules (Basel, Switzerland) · 2023Article
- Rational Design and Production of Bioactive Analogs of Recombinant Human Keratinocyte Growth Factor (rhKGF) with Reduced Aggregation Propensity.The protein journal · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor 2 (FGF2) plays important roles in tissue development and repair. Using heparan sulfates (HS)/heparin as a cofactor, FGF2 binds to FGF receptor (FGFR) and induces downstream signaling pathways, such as ERK pathway, that regulate cellular behavior. In most cell lines, FGF2 signaling displays biphasic dose-response profile, reaching maximal response to intermediate concentrations, but weak response to high levels of FGF2. Recent reports demonstrated that the biphasic cellular response results from competition between binding of FGF2 to HS and FGFR that impinge upon ERK signaling dynamics. However, the role of HS/heparin in FGF signaling has been controversial. Several studies suggested that heparin is not required for FGF-FGFR complex formation and that the main role of heparin is to protect FGF from degradation. In this study, we investigated the relationship between FGF2 stability, heparin dependence and ERK signaling dynamics using FGF2 variants with increased thermal stability (FGF2-STABs). FGF2-STABs showed higher efficiency in induction of FGFR-mediated proliferation, lower affinity to heparin and were less dependent on heparin than wild-type FGF2 (FGF2-wt) for induction of FGFR-mediated mitogenic response. Interestingly, in primary mammary fibroblasts, FGF2-wt displayed a sigmoidal dose-response profile, while FGF2-STABs showed a biphasic response. Moreover, at low concentrations, FGF2-STABs induced ERK signaling more potently and displayed a faster dynamics of full ERK activation and higher amplitudes of ERK signaling than FGF2-wt. Our results suggest that FGF2 stability and heparin dependence are important factors in FGF-FGFR signaling complex assembly and ERK signaling dynamics.
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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 Socratic graph.