ArticleCell communication and signaling : CCS2010
The heparan sulfate co-receptor and the concentration of fibroblast growth factor-2 independently elicit different signalling patterns from the fibroblast growth factor receptor.
Article in Cell communication and signaling : CCS, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
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- State-Dependent FGF Signaling in Satellite Cell-Mediated Skeletal Muscle Regeneration and Pathological Remodeling.Biomolecules · 2026Review
- Structural analysis of the stable form of fibroblast growth factor 2 - FGF2-STAB.Journal of structural biology: X · 2024Article
- An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development.Developmental cell · 2023Article
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- Functions of exogenous FGF signals in regulation of fibroblast to myofibroblast differentiation and extracellular matrix protein expression.Open biology · 2022Review
- Synthetic Heparan Sulfate Hydrogels Regulate Neurotrophic Factor Signaling and Neuronal Network Activity.ACS applied materials & interfaces · 2022Article
- Fibroblast growth factor receptor signalling dysregulation and targeting in breast cancer.Open biology · 2022Review
- FGF2 engineered SPIONs attenuate tumor stroma and potentiate the effect of chemotherapy in 3D heterospheroidal model of pancreatic tumor.Nanotheranostics · 2020Article
- HSV-1 triggers paracrine fibroblast growth factor response from cortical brain cells via immediate-early protein ICP0.Journal of neuroinflammation · 2019Article
- Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling.Molecular systems biology · 2019Article
- Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation.FEBS open bio · 2019Article
- Fibroblast Growth Factor 2 Protein Stability Provides Decreased Dependence on Heparin for Induction of FGFR Signaling and Alters ERK Signaling Dynamics.Frontiers in cell and developmental biology · 2019Article
- Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and FGF2 signalling.Matrix biology : journal of the International Society for Matrix Biology · 2017Article
- Receptor FGFRL1 does not promote cell proliferation but induces cell adhesion.International journal of molecular medicine · 2016Article
- Article
- The calcium phosphate matrix of FGF-2-apatite composite layers contributes to their biological effects.International journal of molecular sciences · 2014Article
- Deciphering the mechanism behind Fibroblast Growth Factor (FGF) induced biphasic signal-response profiles.Cell communication and signaling : CCS · 2014Article
- Biphasic responses in multi-site phosphorylation systems.Journal of the Royal Society, Interface · 2013Article
- Multivalent proteoglycan modulation of FGF mitogenic responses in perivascular cells.Angiogenesis · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe fibroblast growth factor receptor (FGFR) interprets concentration gradients of FGF ligands and structural changes in the heparan sulfate (HS) co-receptor to generate different cellular responses. However, whether the FGFR generates different signals is not known.
resultsWe have previously shown in rat mammary fibroblasts that in cells deficient in sulfation, and so in HS co-receptor, FGF-2 can only stimulate a transient phosphorylation of p42/44 MAPK and so cannot stimulate DNA synthesis. Here we demonstrate that this is because in the absence of HS, FGF-2 fails to stimulate the phosphorylation of the adaptor FGFR substrate 2 (FRS2). In cells possessing the HS co-receptor, FGF-2 elicits a bell-shaped dose response: optimal concentrations stimulate DNA synthesis, but supramaximal concentrations (>/= 100 ng/mL) have little effect. At optimal concentrations (300 pg/mL) FGF-2 stimulates a sustained dual phosphorylation of p42/44 MAPK and tyrosine phosphorylation of FRS2. In contrast, 100 ng/mL FGF-2 only stimulates a transient early peak of p42/44 MAPK phosphorylation and fails to stimulate appreciably the phosphorylation of FRS2 on tyrosine.
conclusionsThese results suggest that the nature of the FGFR signal produced is determined by a combination of the HS co-receptor and the concentration of FGF ligand. Both the phosphorylation of the adaptor FRS2, the kinetics (sustained or transient) of phosphorylation of p42/44(MAPK) are varied, and so differing cellular responses are produced.
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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.