Affinage

FGF2

Fibroblast growth factor 2 · UniProt P09038

Length
288 aa
Mass
30.8 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF2 is a multifunctional growth factor that exists as a secreted 18-kDa isoform signaling through cell-surface FGFR tyrosine kinases and high molecular weight nuclear isoforms that act independently of FGFRs (PMID:18850066). The 18-kDa form reaches the extracellular space through an unconventional, ER/Golgi-independent route: it is recruited to the inner plasma membrane leaflet by PI(4,5)P2, oligomerizes (predominantly as dimers) into membrane-pore translocation intermediates directly visualized in real time, and is captured at the outer leaflet by heparan sulfates (PMID:30470711); cholesterol promotes this secretion by clustering PI(4,5)P2 and raising membrane tension to favor pore formation (PMID:36173379). Once engaged with FGFRs and heparan-sulfate co-receptors, FGF2 drives ERK/MAPK, PI3K, PLCγ, STAT3, and JNK outputs whose kinetics are shaped by competition between FGFR and heparan sulfate proteoglycan binding (PMID:31777174, PMID:15194433). Through ERK, FGF2 governs osteoblast differentiation by phosphorylating Runx2 at Ser-301 to stabilize it and by inducing TAZ to promote TAZ-Runx2 transcription (PMID:20007706, PMID:24125755), and endogenous FGF2 is required for the PTH anabolic response in osteoblasts (PMID:19107841); through other branches it controls satellite-cell activation via a TRPC-Ca2+-NFAT-MyoD axis (PMID:24575047), deactivates hepatic stellate cells by driving JNK/c-JUN-dependent CYGB transcription (PMID:28916723), and stimulates tanycyte proliferation via Cx43 hemichannel ATP release and purinergic P2Y1 signaling (PMID:32936929). FGF2 is a central driver of pathologic angiogenesis and tumor progression, acting through STAT3, reciprocal PDGFR/FGFR cross-induction, and an integrin αvβ3-binding interface required for ERK activation and neovascularization (PMID:17909625, PMID:31449793, PMID:28302677). Nuclear FGF2 complexes with API5 through a cryptic nuclear localization sequence to regulate mRNA export via the TREX and eIF4E/LRPPRC pathways (PMID:32383752), and intracellularly translocated FGF2 exerts FGFR-independent anti-apoptotic activity (PMID:30099027). Its activity is tuned by extracellular interactors including heparanase-remodeled heparan sulfate (PMID:16867222), CCN2 (PMID:21914781), PLAP-1/Asporin (PMID:26239644), and VEGF-B, which inhibits FGF2/FGFR1 signaling by inducing FGFR1/VEGFR1 complexes (PMID:37591843).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 Medium

    Established that FGF2 can act as a growth-arrest signal rather than only a mitogen, defining how it imposes G1 arrest through Ras/ERK in chondrocytes.

    Evidence Chemical inhibitors, dominant-negative Ras, and cyclin-CDK complex analysis in RCS chondrocytes

    PMID:15194433

    Open questions at the time
    • Cell-type basis for arrest versus proliferation outputs not resolved
    • Did not address nuclear FGF2 isoform contributions
  2. 2009 High

    Resolved how FGF2-ERK signaling is converted into osteoblast differentiation by identifying Runx2 Ser-301 as the ERK phosphorylation site controlling Runx2 stability.

    Evidence Site-directed mutagenesis, constitutively active MEK, and ERK inhibition with biochemical readouts

    PMID:20007706

    Open questions at the time
    • Kinase-substrate directness in vivo not shown
    • Other ERK substrates in osteogenesis not mapped
  3. 2009 Medium

    Distinguished FGFR-independent nuclear HMW FGF2 isoforms from the FGFR-signaling 18-kDa form, framing FGF2 as a dual intracellular/extracellular factor.

    Evidence Review synthesizing cell fractionation, isoform expression, and nuclear localization studies

    PMID:18850066

    Open questions at the time
    • Molecular mechanism of HMW nuclear function unspecified
    • Trafficking determinants not defined
  4. 2009 Medium

    Showed endogenous FGF2 is necessary for the PTH anabolic program, placing FGF2 as a required cofactor in hormone-driven osteoblast signaling.

    Evidence Fgf2-/- versus Fgf2+/+ osteoblasts plus siRNA silencing with Runx2/CREB/cyclin-CDK readouts

    PMID:19107841

    Open questions at the time
    • Whether intracrine or autocrine FGF2 mediates the requirement unresolved
    • Receptor subtype not defined
  5. 2013 Medium

    Added a transcriptional arm to FGF2-driven osteogenesis by showing ERK-induced TAZ enables TAZ-Runx2 cooperation.

    Evidence shRNA knockdown, ERK inhibition, nuclear fractionation, and TAZ-Runx2 Co-IP

    PMID:24125755

    Open questions at the time
    • Mechanism linking ERK to TAZ induction not detailed
    • Single cell-system validation
  6. 2014 Medium

    Defined distinct effector branches downstream of FGF2 in non-bone tissues — TRPC-Ca2+-NFAT for satellite cell activation.

    Evidence Calcium imaging, TRPC blocker, and NFAT/MyoD readouts in satellite cells

    PMID:24575047

    Open questions at the time
    • FGFR subtype coupling TRPC not identified
    • Direct channel activation mechanism not shown
  7. 2017 High

    Identified a JNK/c-JUN transcriptional output through which FGF2 deactivates myofibroblastic hepatic stellate cells by driving CYGB.

    Evidence ChIP localizing phospho-c-JUN to the CYGB promoter, siRNA, JNK inhibition, and in vivo bile duct ligation

    PMID:28916723

    Open questions at the time
    • Upstream coupling from FGFR to JNK not mapped
    • Reversibility of HSC deactivation not addressed
  8. 2017 Medium

    Mapped an integrin αvβ3-binding interface on FGF2 required for ERK activation and angiogenesis, yielding dominant-negative antagonist mutants.

    Evidence Site-directed mutagenesis at Lys-119/Arg-120 and Lys-125 with binding, signaling, and in vivo angiogenesis assays

    PMID:28302677

    Open questions at the time
    • Structural integrin-FGF2 complex not determined
    • Relationship to FGFR engagement not fully separated
  9. 2018 High

    Provided the structural basis for nuclear FGF2 by solving the API5-FGF2 complex and identifying a cryptic NLS, linking nuclear FGF2 to mRNA export.

    Evidence X-ray crystallography, Co-IP, and mRNA export functional assays implicating TREX and eIF4E/LRPPRC

    PMID:32383752

    Open questions at the time
    • In vivo physiological role of API5-FGF2 mRNA export unclear
    • Isoform specificity of nuclear import not fully resolved
  10. 2018 High

    Directly visualized the unconventional secretion mechanism, showing FGF2 oligomerizes and forms membrane-pore translocation intermediates at the plasma membrane.

    Evidence Live-cell TIRF microscopy with dual-channel imaging and oligomer detection establishing PI(4,5)P2 and heparan sulfate dependence

    PMID:30470711

    Open questions at the time
    • Pore stoichiometry and resealing dynamics not fully defined
    • In vivo relevance of measured kinetics unaddressed
  11. 2018 Medium

    Separated FGFR-independent intracellular function of FGF2 by showing translocated FGF2 protects against apoptosis independent of receptor kinase activity.

    Evidence FGFR kinase inhibitors, kinase-dead FGFR1, and endosomal translocation inhibitors in apoptosis assays

    PMID:30099027

    Open questions at the time
    • Intracellular anti-apoptotic effector(s) unidentified
    • Mechanism of endosome-to-cytosol translocation incomplete
  12. 2019 Medium

    Quantitatively explained variability in FGF2-ERK signaling as a consequence of FGFR/HSPG co-receptor competition with intracellular feedback.

    Evidence Microfluidic temporal perturbations, live-cell ERK biosensors, and Bayesian model selection in PC12 cells

    PMID:31777174

    Open questions at the time
    • Molecular identity of the intracellular feedback node not specified
    • Generalizability beyond PC12 cells untested
  13. 2022 High

    Explained how membrane lipid composition gates FGF2 secretion, showing cholesterol clusters PI(4,5)P2 to promote oligomerization and pore formation.

    Evidence Live-cell imaging, atomistic MD simulations, and membrane tension/binding assays

    PMID:36173379

    Open questions at the time
    • Physiological regulation of cholesterol-driven secretion in vivo not shown
    • Quantitative contribution relative to PI(4,5)P2 alone not parsed
  14. 2023 Medium

    Identified VEGF-B as an endogenous inhibitor of FGF2/FGFR1 signaling acting by inducing FGFR1/VEGFR1 receptor complexes.

    Evidence Binding assays, receptor Co-IP, ERK phosphorylation, and in vitro/in vivo angiogenesis models

    PMID:37591843

    Open questions at the time
    • Structural basis of the FGFR1/VEGFR1 complex not resolved
    • Context-dependence on FGFR1 abundance needs broader validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the FGFR-dependent surface signaling, FGFR-independent intracellular protection, and nuclear mRNA-export functions of FGF2 are coordinated within a single cell remains unresolved.
  • No integrated model linking isoform partitioning to functional output
  • Quantitative balance between unconventional secretion and intracrine retention unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005576 extracellular region 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-9609507 Protein localization 2 R-HSA-8953854 Metabolism of RNA 1
Partners
API5CCN2FGFR1HEPARAN SULFATE PROTEOGLYCANINTEGRIN ALPHAVBETA3PLAP-1/ASPNVEGFB
Complex memberships
FGF2-API5 nuclear complexFGF2-FGFR1 receptor complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Crystal structure of the API5-FGF2 complex was determined, revealing critical residues driving the protein interaction. The structure provided a structural basis for the nuclear localization of the FGF2 isoform lacking a canonical nuclear localization signal and identified a cryptic nuclear localization sequence in FGF2. The API5-FGF2 interaction regulates mRNA nuclear export through both the TREX and eIF4E/LRPPRC mRNA export complexes. X-ray crystallography, Co-IP, mRNA export functional assays Nucleic acids research High 32383752
2018 FGF2 undergoes unconventional secretion by direct membrane translocation at the plasma membrane. Live-cell TIRF microscopy directly visualized individual FGF2 membrane translocation events with an average duration of ~200 ms. FGF2 forms oligomers (predominantly dimers) at the inner plasma membrane leaflet; these oligomers form membrane pores that serve as dynamic translocation intermediates. The process requires PI(4,5)P2-mediated recruitment at the inner leaflet and heparan sulfates capturing FGF2 at the outer leaflet. Live-cell TIRF microscopy, simultaneous dual-channel imaging, fluorescence-based oligomer detection The Journal of cell biology High 30470711
2022 Cholesterol promotes clustering of PI(4,5)P2 at the plasma membrane, thereby enhancing FGF2 binding and oligomerization at the inner leaflet and facilitating FGF2 membrane translocation during unconventional secretion. Mechanistically, cholesterol increases PI(4,5)P2 head group visibility, induces PI(4,5)P2 clustering that drives FGF2 oligomerization, and increases membrane tension to facilitate lipidic pore formation. Live-cell imaging, atomistic molecular dynamics simulations, membrane tension experiments, lipid bilayer binding assays The Journal of cell biology High 36173379
2009 High molecular weight (HMW) FGF2 isoforms are retained in the nucleus and act independently of FGF receptors (FGFR), in contrast to the 18 kDa secreted isoform that signals through cell-surface FGFR tyrosine kinases. HMW FGF2 undergoes distinct intracellular trafficking and has nuclear functions. Review synthesizing cell fractionation, isoform-specific expression, and nuclear localization studies Cellular and molecular life sciences : CMLS Medium 18850066
2011 FGF2 binds directly to Chlamydia trachomatis elementary bodies (EBs) and functions as a bridging molecule to facilitate EB interaction with FGFR on the host cell surface. Upon EB binding, FGFR is locally activated and contributes to bacterial uptake into non-phagocytic cells. C. trachomatis infection stimulates fgf2 transcription and enhances FGF2 production/release through a pathway requiring bacterial protein synthesis and Erk1/2 activation but independent of FGFR activation. Direct binding assays, FGFR activation assays, siRNA knockdown, pharmacological inhibition of FGFR and Erk1/2 PLoS pathogens Medium 21998584
2014 Nuclear FGFR1 and FGF2 co-localize in the nucleus of activated pancreatic stellate cells (PSCs) at the invasive front of pancreatic cancer. Abrogation of nuclear FGF2 and FGFR1 in PSCs (via FGFR inhibition or RNAi) abolished cancer cell invasion in organotypic co-cultures, demonstrating that nuclear FGF2/FGFR1 signaling in PSCs drives invasion. IHC localization, RNAi, chemical FGFR inhibition, organotypic co-culture invasion assays EMBO molecular medicine Medium 24503018
2019 FGF2 signals through FGFR1/2 on bone marrow stromal cells to regulate secretion of FGF2-containing exosomes. These exosomes are endocytosed by leukemia cells and protect them from tyrosine kinase inhibitors. FGFR inhibition or Fgf2 gene silencing in stromal cells significantly decreased exosome secretion and reduced stromal protection of leukemia cells. Exosome isolation and characterization, Co-IP, FGFR inhibition/siRNA knockdown, Fgf2-/- mouse transplant model, TKI resistance assays eLife Medium 30720426
2009 FGF2 activates ERK MAP kinase, which phosphorylates Runx2 at Ser-301, leading to increased Runx2 acetylation, decreased ubiquitination, and protein stabilization. This ERK-mediated post-translational modification of Runx2 underlies FGF2-stimulated osteoblast differentiation. Western blotting, site-directed mutagenesis (Ser-301), constitutively active MEK overexpression, ERK inhibitor treatment, in silico analysis of ERK phosphorylation sites The Journal of biological chemistry High 20007706
2013 FGF2 stimulates osteogenic differentiation by inducing TAZ expression via ERK activation. FGF2 increases TAZ mRNA expression and promotes nuclear localization of TAZ, facilitating TAZ-Runx2 interaction and Runx2-mediated gene transcription. Depletion of TAZ via shRNA blocked FGF2-mediated osteogenic differentiation. shRNA knockdown, ERK inhibition, nuclear fractionation, Co-IP of TAZ-Runx2, gene expression analysis Bone Medium 24125755
2007 FGF2 triggers transcriptional upregulation of PDGFR-alpha and -beta in endothelial cells, conferring hyperresponsiveness to PDGF-BB. Reciprocally, PDGF-BB upregulates FGFR1 promoter activity in vascular smooth muscle cells, making them responsive to FGF2. This reciprocal interaction promotes disorganized neovascularization and tumor metastasis. Promoter activity assays, receptor expression analysis, tumor co-overexpression models in mice, in vivo angiogenesis and metastasis assays The Journal of clinical investigation Medium 17909625
2019 FGF2 regulates pathologic choroidal neovascularization via STAT3 activation. In ex vivo choroidal sprouting and in vivo CNV models, FGF2 was identified as the essential FGF ligand for FGFR1/2-dependent angiogenesis, acting through STAT3 pathway activation. Ex vivo choroidal sprouting assay, in vivo CNV mouse model, STAT3 pathway inhibition Experimental eye research Medium 31449793
2011 CCN2 (connective tissue growth factor) directly binds to FGF2 via its C-terminal (CT) module with a dissociation constant of 5.5 nM as measured by surface plasmon resonance. This interaction nullifies FGF2-induced chondrocyte proliferation and MMP9/MMP13 production. The CT module decreased ERK1/2, p38 MAPK, and JNK phosphorylation induced by FGF2. Separately, full-length CCN2 (not CT alone) also binds FGF receptor 1 (Kd ~362 nM). Solid-phase binding assay, Co-IP/Western blot, surface plasmon resonance (SPR), cell proliferation assay, phosphorylation analysis Endocrinology High 21914781
2015 PLAP-1/Asporin directly binds FGF2 and promotes formation of the FGF2-FGFR1 complex, positively regulating FGF2 activity. Plap-1-/- mouse embryonic fibroblasts showed defective responses to FGF2, which were rescued by Plap-1 transfection. Immunocytochemistry showed reduced FGF2-FGFR1 co-localization in Plap-1-/- MEFs. Binding assays, genetic knockout (Plap-1-/- mice), transfection rescue, immunocytochemistry Journal of dental research Medium 26239644
2023 VEGF-B binds to FGFR1 and induces FGFR1/VEGFR1 complex formation, suppressing FGF2-induced ERK activation and FGF2-driven angiogenesis and tumor growth. VEGF-B functions as an endogenous inhibitor of the FGF2/FGFR1 pathway when FGFR1 is abundantly expressed. Binding assays, receptor co-immunoprecipitation (FGFR1/VEGFR1 complex), ERK phosphorylation assays, in vitro and in vivo angiogenesis models Signal transduction and targeted therapy Medium 37591843
2006 Heparanase (HPSE) modulates FGF2 binding and signaling in melanoma cells by remodeling heparan sulfate (HS) proteoglycans. Low HPSE concentrations enhanced FGF2 binding and enabled ERK and FAK phosphorylation in response to FGF2 (which was absent without HPSE treatment). Higher HPSE concentrations inhibited FGF2 binding. Soluble HPSE-degraded HS enhanced FGF2-induced ERK but not FAK phosphorylation, demonstrating differential modulation of FGF2 downstream signals. FGF2 binding assays, ERK/FAK phosphorylation assays, angiogenesis assays, HPSE dose-response experiments Neoplasia (New York, N.Y.) Medium 16867222
2014 FGF2 promotes resistance to imatinib in CML via the FGF receptor 3/RAS/c-RAF/MAPK pathway. FGF2 was uniquely capable of promoting growth in short- and long-term resistance assays, and this resistance could be overcome with ponatinib, a multikinase inhibitor targeting BCR-ABL and FGFR. In vitro growth/resistance assays, pathway inhibitor experiments, clinical patient bone marrow immunohistochemistry, pharmacological reversal Blood Medium 24408322
2014 API5 mediates tumor immune escape by upregulating FGF2 signaling through a FGFR1/PKCδ/ERK effector pathway that triggers degradation of the pro-apoptotic molecule BIM. Blockade of FGF2, PKCδ, or ERK phenocopied API5 silencing in restoring immune sensitivity. RNAi silencing, pathway inhibitors (FGF2, PKCδ, ERK blockade), apoptosis assays with antigen-specific T cells Cancer research Medium 24769442
2017 FGF2 regulates cytoglobin (CYGB) gene expression and deactivation of myofibroblastic hepatic stellate cells (HSCs) via JNK signaling. FGF2 triggered rapid phosphorylation of JNK and c-JUN; chromatin immunoprecipitation showed phospho-c-JUN binds to the CYGB promoter at -218 to -222 bases from the transcription initiation site. JNK inhibition and c-JUN siRNA abrogated FGF2-mediated CYGB induction. Western blot (JNK/c-JUN phosphorylation), ChIP assay (phospho-c-JUN at CYGB promoter), siRNA knockdown, JNK inhibitor, in vivo bile duct ligation model The Journal of biological chemistry High 28916723
2010 Protein kinase C-delta (PKCδ) physically interacts with connexin43 (Cx43) during FGF2 signaling in osteoblasts. PKCδ preferentially co-precipitates phosphorylated Cx43, and pull-down assays demonstrated that PKCδ associates with the C-terminal tail of Cx43. Cx43 serves as a direct docking platform for PKCδ recruitment to affect FGF2 signaling. Co-immunoprecipitation, pull-down assay with Cx43 C-terminal tail, immunofluorescent co-detection BMC biochemistry Medium 20338032
2019 FGF2-induced ERK signaling dynamics in PC12 cells emerge through an intracellular feedback mechanism combined with competition of FGF2 binding to FGFRs and heparan sulfate proteoglycan (HSPG) co-receptors. This competition produces a distinct population-level distribution of transient/sustained ERK signaling states, revealed by temporally controlled microfluidic growth factor perturbations and Bayesian parameter inference. Microfluidics-based temporal perturbation, live-cell ERK biosensor imaging, Bayesian parameter inference/model selection Molecular systems biology Medium 31777174
2004 FGF2 induces G1 cell cycle arrest in RCS chondrocytes through a Ras/ERK pathway-dependent mechanism. FGF2 activated PLCγ, PKB, ERK, and p38 MAPK. Chemical inhibition of FGFR3 or MEK1/2 antagonized FGF2-mediated growth arrest. Dominant-negative Ras partially reversed growth inhibition. At the molecular level, FGF2-induced arrest involved disintegration of cyclin D3-cdk6 complex and increased association of p21(WAF1) and p27(Kip1) with cyclin-cdk2 and cyclin-cdk4 complexes, inhibiting their kinase activities and leading to underphosphorylation of p107 and p130. Chemical inhibitors (FGFR3, MEK), dominant-negative Ras expression, cell cycle analysis, kinase complex immunoprecipitation, kinase activity assays Experimental cell research Medium 15194433
2014 FGF2 activates TRPC channels in satellite cells, leading to increased intracellular calcium ([Ca2+]i). This calcium elevation induces nuclear translocation of NFATc3 and NFATc2, and increases the number of MyoD-positive cells. These effects were antagonized by the TRPC channel blocker SKF 96365, identifying a pathway: FGF2 → TRPC → [Ca2+]i elevation → NFAT nuclear translocation → MyoD expression/satellite cell activation. Immunostaining, live-cell calcium imaging with X-rhod-1 dye, TRPC blocker (SKF 96365), nuclear translocation imaging, MyoD counting Frontiers in physiology Medium 24575047
2018 Translocated intracellular FGF2 (endocytosed from outside the cell) protects cells against apoptosis independently of FGFR activation and downstream signaling. This anti-apoptotic activity was abolished by inhibitors of FGF2 translocation from endosomes to the cell interior, but not by potent FGFR kinase inhibitors or kinase-dead FGFR1 mutants. FGFR inhibitor treatment, kinase-dead FGFR1 mutant expression, endosomal translocation inhibitors, apoptosis assays (serum starvation/staurosporine models) Journal of molecular biology Medium 30099027
2009 FGF2 stimulates SDF-1 expression in Sertoli cells via FGFR4-dependent upregulation of Erm transcription factor. Erm knockdown by siRNA decreased Sdf-1 levels. EMSA revealed ERM directly binds to a specific Ets binding site (-846 to -851 nt region) in the Sdf-1 promoter. FGFR4, expressed in TM4 Sertoli cells but not ST2 stromal cells, mediates the differential FGF2 response. siRNA knockdown, FGFR subtype analysis, FGFR blocking experiments, EMSA, Sdf-1 promoter activity assay Journal of cellular physiology Medium 19301256
2012 HoxA10 directly transcriptionally activates the FGF2 gene in myeloid cells via two cis-elements in the proximal FGF2 promoter. HoxA10-driven FGF2 production induces a PI3K-dependent increase in β-catenin, causing autocrine stimulation of myeloid progenitor proliferation. Promoter reporter assays with cis-element identification, ChIP-type analysis, FGF2 ELISA, PI3K inhibitor, β-catenin western blotting, proliferation assays The Journal of biological chemistry Medium 22493287
2023 YY1 lactylation at lysine 183 (K183), regulated by p300 acetyltransferase, directly enhances FGF2 transcription in microglia under hypoxia, promoting retinal neovascularization. YY1 K183 mutation eliminated the enhanced FGF2 transcription and angiogenic effects. p300 inhibitor A485 suppressed vascularization in vivo and in vitro. Lactylation site identification by mass spectrometry, site-directed mutagenesis (K183), p300 overexpression/inhibition (A485), FGF2 promoter activity assays, in vivo OIR model Genome biology Medium 37085894
2021 ONECUT2 directly binds the FGF2 promoter and transcriptionally upregulates FGF2 expression in HCC. FGF2 in turn upregulates ONECUT2 through the FGFR1/ERK/ELK1 pathway, forming a positive feedback loop. FGF2 knockdown inhibited ONECUT2-mediated HCC metastasis. ChIP assay (ONECUT2 binding FGF2 promoter), siRNA/shRNA knockdown, FGFR1 inhibitor (PD173074), ERK pathway analysis, metastasis assays Cell death & disease Medium 34839358
2017 FGF2 mutants with substitutions at Lys-119/Arg-120 and Lys-125 (K119E/R120E and K125E) in the predicted integrin αvβ3 binding interface show reduced integrin binding and are defective in ERK1/2 activation and DNA synthesis. These integrin-binding defective FGF2 mutants act as dominant-negative antagonists, suppressing FGF2 signaling, tube formation, aortic ring sprouting, and in vivo angiogenesis. Integrin binding assays, site-directed mutagenesis, ERK1/2 phosphorylation assays, DNA synthesis assay, tube formation, aortic ring assay, in vivo angiogenesis Bioscience reports Medium 28302677
2021 FGF2 inhibits thermogenesis in brown and beige adipocytes via autocrine/paracrine mechanisms. Exogenous FGF2 suppresses PGC-1α and PPARγ expression, leading to UCP1 suppression in brown and beige adipocytes. Co-IP experiments and ChIP assays were used to elucidate the mechanism. FGF2-KO mice show enhanced UCP1 expression and thermogenic capacity. FGF2-KO mice, Co-IP, ChIP, luciferase reporter assay, FGF2 supplementation in vitro, FGFR inhibitor, PPARγ agonist, PGC-1α lentivirus Molecular metabolism Medium 34710640
2022 FGF-2 signaling in nasopharyngeal carcinoma promotes pericyte-specific expression of CXCL14 via FGFR1/AHR signaling. Pericyte-derived CXCL14 recruits macrophages and promotes their polarization toward an M2-like phenotype. Genetic knockdown of FGF2 or pericyte depletion blocked CXCL14 expression and tumor-associated macrophage infiltration. Gain- and loss-of-function (FGF2 knockdown, pericyte depletion), FGFR1/AHR pathway analysis, xenograft mouse models JCI insight Medium 35439170
2020 FGF2-induced tanycyte proliferation requires connexin 43 (Cx43) hemichannel opening and subsequent purinergic signaling. FGF2 exposure opens tanycytic Cx43 hemichannels, enabling ATP release to the extracellular milieu. Extracellular ATP activates P2Y1 receptors to drive cell division. In vivo continuous infusion of FGF2 with a Cx43 HC inhibitor into the third ventricle blocked β-tanycyte proliferation. BrdU incorporation, Cx43 HC inhibitors (in vitro and in vivo), P2Y1 receptor inhibitors, ATP release measurement, ICV infusion in rats Journal of neurochemistry Medium 32936929
2021 YAP is translocated to the nucleus after radiation in glioma cells, where it promotes FGF2 expression and secretion. Secreted FGF2 then activates the MAPK-ERK pathway to promote DNA damage repair and radioresistance. FGF2 was identified as a novel direct transcriptional target gene of YAP. YAP nuclear translocation imaging, FGF2 promoter ChIP/reporter assays, pharmacological inhibition of YAP-FGF2-MAPK axis, intracranial xenograft models Oncogene Medium 34127812
2009 Endogenous FGF-2 is required for parathyroid hormone (PTH) anabolic effects on osteoblasts. PTH increased Runx-2 protein expression and nuclear accumulation, and phospho-CREB levels in Fgf2+/+ but not Fgf2-/- osteoblasts. FGF-2 silencing in Fgf2+/+ osteoblasts blocked PTH-stimulated Runx-2 and CREB phosphorylation. PTH increased cyclinD1-cdk4/6 in Fgf2+/+ but not Fgf2-/- osteoblasts. Fgf2-/- and Fgf2+/+ osteoblasts, FGF-2 siRNA silencing, Western blot for Runx-2/p-CREB/cyclin-CDK complexes, immunocytochemistry Journal of cellular physiology Medium 19107841

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 343 10864959
2023 YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2. Genome biology 252 37085894
2007 Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. The Journal of clinical investigation 244 17909625
2004 Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis and cartilage 244 15564063
2013 MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth. Cancer letters 161 23352645
2016 Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies. Oncotarget 154 27007053
2019 VEGF and FGF-2: Promising targets for the treatment of respiratory disorders. Respiratory medicine 144 31421589
2016 MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2. Nature microbiology 130 27572168
2014 Nuclear translocation of FGFR1 and FGF2 in pancreatic stellate cells facilitates pancreatic cancer cell invasion. EMBO molecular medicine 129 24503018
2009 A new role for FGF2 as an endogenous inhibitor of anxiety. The Journal of neuroscience : the official journal of the Society for Neuroscience 127 19439615
2001 TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis. Development (Cambridge, England) 127 11245570
2009 Inflammatory cells and chemokines sustain FGF2-induced angiogenesis. European cytokine network 115 19541589
2016 miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell death & disease 109 27362808
2009 FGF2-activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization. The Journal of biological chemistry 109 20007706
1997 FGF-2 converts mature oligodendrocytes to a novel phenotype. Journal of neuroscience research 109 9373031
1998 Regulation of astrocyte GFAP expression by TGF-beta1 and FGF-2. Glia 91 9537840
2005 Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development. Developmental dynamics : an official publication of the American Association of Anatomists 90 15765505
2013 Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding. PloS one 87 23437109
2007 VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis. BMC musculoskeletal disorders 78 17204151
2006 FGF2 binding, signaling, and angiogenesis are modulated by heparanase in metastatic melanoma cells. Neoplasia (New York, N.Y.) 74 16867222
1999 FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. The Journal of urology 73 10411093
2000 Programmed cell death in the developing heart: regulation by BMP4 and FGF2. Developmental dynamics : an official publication of the American Association of Anatomists 70 10767083
2014 MiR-152 suppresses the proliferation and invasion of NSCLC cells by inhibiting FGF2. Experimental & molecular medicine 69 25190353
2013 FGF2 stimulates osteogenic differentiation through ERK induced TAZ expression. Bone 67 24125755
2006 Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice. Biochemical and biophysical research communications 64 16455048
2016 miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage. Journal of molecular medicine (Berlin, Germany) 63 26816250
2022 FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis. JCI insight 62 35439170
2004 FGF2 inhibits proliferation and alters the cartilage-like phenotype of RCS cells. Experimental cell research 62 15194433
2005 FGF-2, IL-1beta and TGF-beta regulate fibroblast expression of S100A8. The FEBS journal 61 15943814
2019 FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells. eLife 58 30720426
2015 miR-195 Inhibits EMT by Targeting FGF2 in Prostate Cancer Cells. PloS one 58 26650737
2009 High molecular weight FGF2: the biology of a nuclear growth factor. Cellular and molecular life sciences : CMLS 58 18850066
2023 VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway. Signal transduction and targeted therapy 55 37591843
2018 FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche. Stem cell reports 54 29681540
2009 Endogenous FGF-2 is critically important in PTH anabolic effects on bone. Journal of cellular physiology 54 19107841
2007 Creating a neurogenic environment: the role of BDNF and FGF2. Molecular and cellular neurosciences 53 17656107
2011 Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection. PLoS pathogens 51 21998584
2011 HSulf-1 modulates FGF2- and hypoxia-mediated migration and invasion of breast cancer cells. Cancer research 50 21266348
2009 Retinal expression of Fgf2 in RCS rats with subretinal microphotodiode array. Investigative ophthalmology & visual science 46 19264883
2017 The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis. Bioscience reports 45 28302677
2014 API5 confers tumoral immune escape through FGF2-dependent cell survival pathway. Cancer research 45 24769442
2021 Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair. Oncogene 44 34127812
2018 FGF2-dependent mesenchyme and laminin-111 are niche factors in salivary gland organoids. Journal of cell science 44 29361536
2011 Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes. Endocrinology 44 21914781
2021 ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY. Cell death & disease 42 34839358
2014 Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations. Blood 42 24408322
2013 Identification and characterization of FGF2-dependent mRNA: microRNA networks during lens fiber cell differentiation. G3 (Bethesda, Md.) 42 24142921
2017 Fibroblast growth factor 2 (FGF2) regulates cytoglobin expression and activation of human hepatic stellate cells via JNK signaling. The Journal of biological chemistry 40 28916723
2013 Cooperative effects of FGF-2 and VEGF-A in periodontal ligament cells. Journal of dental research 40 24186558
2015 Biphasic effects of FGF2 on adipogenesis. PloS one 39 25790378
2003 Expression of CD137 and its ligand in human neurons, astrocytes, and microglia: modulation by FGF-2. Journal of neuroscience research 39 13130507
2020 FGF2 and IL-1β - explorers of unconventional secretory pathways at a glance. Journal of cell science 38 33154173
1991 Basic fibroblast growth factor (FGFb) and epidermal growth factor (EGF) receptor messenger RNA production in human lacrimal gland. Investigative ophthalmology & visual science 38 1894478
2014 Malondialdehyde mediates oxidized LDL-induced coronary toxicity through the Akt-FGF2 pathway via DNA methylation. Journal of biomedical science 37 24490960
2007 FGF2 in asthmatic airway-smooth-muscle-cell hyperplasia. Trends in molecular medicine 37 18055262
2021 FGF2/FGFR signaling promotes cumulus-oocyte complex maturation in vitro. Reproduction (Cambridge, England) 36 33434172
2017 FGF2 cooperates with IL-17 to promote autoimmune inflammation. Scientific reports 36 28765647
2013 FGF2 and FGFR1 signaling regulate functional recovery following cuprizone demyelination. Neuroscience letters 36 23684572
2012 HoxA10 protein regulates transcription of gene encoding fibroblast growth factor 2 (FGF2) in myeloid cells. The Journal of biological chemistry 36 22493287
2008 Expression analysis of VEGFA, FGF2, TGFbeta1, EGF and IGF1 in human nasal polyposis. Oncology reports 36 18202785
2020 Regulation of mRNA export through API5 and nuclear FGF2 interaction. Nucleic acids research 35 32383752
2019 FGF2-induced STAT3 activation regulates pathologic neovascularization. Experimental eye research 35 31449793
2018 Single event visualization of unconventional secretion of FGF2. The Journal of cell biology 35 30470711
2019 Temporal perturbation of ERK dynamics reveals network architecture of FGF2/MAPK signaling. Molecular systems biology 34 31777174
2010 Interaction of connexin43 and protein kinase C-delta during FGF2 signaling. BMC biochemistry 33 20338032
2018 FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis and lung cancer. Oncology letters 32 30013642
2016 FGF2 Prevents Sunitinib-Induced Cardiotoxicity in Zebrafish and Cardiomyoblast H9c2 Cells. Cardiovascular toxicology 32 25701259
2021 Multiple Therapeutic Applications of RBM-007, an Anti-FGF2 Aptamer. Cells 31 34203430
2016 FGF2 antagonizes aberrant TGFβ regulation of tropomyosin: role for posterior capsule opacity. Journal of cellular and molecular medicine 31 27976512
2014 FGF2 activates TRPC and Ca(2+) signaling leading to satellite cell activation. Frontiers in physiology 31 24575047
2001 FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma. International journal of cancer 31 11745459
2018 FGF-2 promotes osteocyte differentiation through increased E11/podoplanin expression. Journal of cellular physiology 30 29215722
2020 FGF2: a novel druggable target for glioblastoma? Expert opinion on therapeutic targets 28 32174197
2009 The role of FGF-2 in renal fibrogenesis. Frontiers in bioscience (Scholar edition) 28 19482688
2022 FGF2 Is Protective Towards Cisplatin-Induced KGN Cell Toxicity by Promoting FTO Expression and Autophagy. Frontiers in endocrinology 27 35784556
2019 Effects of FGF2/FGFR1 Pathway on Expression of A1 Astrocytes After Infrasound Exposure. Frontiers in neuroscience 27 31130839
2018 Translocation of Exogenous FGF1 and FGF2 Protects the Cell against Apoptosis Independently of Receptor Activation. Journal of molecular biology 27 30099027
2010 Signaling pathways implicated in PGF2alpha effects on Fgf2+/+ and Fgf2-/- osteoblasts. Journal of cellular physiology 27 20432442
2009 FGF2 stimulates SDF-1 expression through the Erm transcription factor in Sertoli cells. Journal of cellular physiology 27 19301256
2008 Neonatal FGF2 alters cocaine self-administration in the adult rat. Pharmacology, biochemistry, and behavior 27 19014962
2013 Up-regulated cten by FGF2 contributes to FGF2-mediated cell migration. Molecular carcinogenesis 26 23625726
2020 The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway. Journal of neurochemistry 25 32936929
2021 Effect of fibronectin, FGF-2, and BMP4 in the stemness maintenance of BMSCs and the metabolic and proteomic cues involved. Stem cell research & therapy 23 33676544
2019 Effect of Testosterone on FGF2, MRF4, and Myostatin in Hypogonadotropic Hypogonadism: Relevance to Muscle Growth. The Journal of clinical endocrinology and metabolism 23 30629183
2015 PLAP-1/Asporin Positively Regulates FGF-2 Activity. Journal of dental research 23 26239644
2018 The FGF2 aptamer inhibits the growth of FGF2-FGFR pathway driven lung cancer cells. Biochemical and biophysical research communications 22 30005872
2006 Modulation of antigenic phenotype in cultured human osteoblast-like cells by FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma. Bioscience reports 22 17029006
2004 Coexpression and regulation of the FGF-2 and FGF antisense genes in leukemic cells. Leukemia research 22 15725477
2020 TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness. PloS one 21 33206726
2016 Stage-specific roles of FGF2 signaling in human neural development. Stem cell research 21 27608170
2021 FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis. Molecular metabolism 20 34710640
2020 NEAT1 Knockdown Inhibits Keloid Fibroblast Progression by miR-196b-5p/FGF2 Axis. The Journal of surgical research 20 33162101
2018 FGF2 Enhances Odontoblast Differentiation by αSMA+ Progenitors In Vivo. Journal of dental research 20 29649366
2010 Influence of FGF2 and PEG hydrogel matrix properties on hMSC viability and spreading. Journal of biomedical materials research. Part A 20 19768790
2024 Dihydroartemisinin inhibited vasculogenic mimicry in gastric cancer through the FGF2/FGFR1 signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 39214017
2018 Linc-RAM is required for FGF2 function in regulating myogenic cell differentiation. RNA biology 19 29364044
2000 Particle irradiation induces FGF2 expression in normal human lens cells. Radiation research 19 11025644
2015 FGF2 Overrides TGFβ1-Driven Integrin ITGA11 Expression in Human Dermal Fibroblasts. Journal of cellular biochemistry 18 26403263
2022 Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2. The Journal of cell biology 17 36173379
2018 Increased High Molecular Weight FGF2 in Endocrine-Resistant Breast Cancer. Hormones & cancer 17 29956066

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