Affinage

FGF1

Fibroblast growth factor 1 · UniProt P05230

Length
155 aa
Mass
17.5 kDa
Annotated
2026-04-28
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF1 is a universally-acting fibroblast growth factor that signals through all FGFR splice isoforms in a heparan sulfate-dependent manner to regulate cell proliferation, differentiation, angiogenesis, neuroprotection, and glucose metabolism. FGF1 forms ternary 2:2:1 FGF1:FGFR:heparin signaling complexes in which heparin primarily stabilizes the inherently unstable FGF1 protein rather than directly bridging FGF1–FGFR interaction, and its N-terminal residues (Phe-16, Asn-22, Tyr-23) confer unique pan-FGFR binding plasticity (PMID:19574212, PMID:22057274, PMID:16219767). Beyond canonical receptor tyrosine kinase signaling, FGF1 directly binds integrin αvβ3 to drive proliferative and migratory responses independently of FGFR kinase activation (PMID:18441324), is secreted via a non-classical Cu²⁺/S100A13/SphK1/AHNAK2-dependent export pathway (PMID:14625381, PMID:17643421, PMID:25560297), and undergoes PI3K-dependent retrograde nuclear translocation where it exerts intracrine neurotrophic and anti-apoptotic functions regulated by nucleolin-dependent PKCδ phosphorylation and nuclear export (PMID:10766827, PMID:19765618, PMID:24595027). FGF1 lowers blood glucose through FGFR1-mediated suppression of adipose lipolysis via PDE4D activation, a mechanism distinct from insulin's PDE3B pathway, and drives compensatory β-cell differentiation in response to overnutrition (PMID:34986332, PMID:25043058, PMID:26420862).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1991 High

    Establishing that FGF1 binds heparan sulfate proteoglycans as high-affinity co-receptors resolved how FGF1 is presented at the cell surface for signaling.

    Evidence Affinity labeling with ¹²⁵I-aFGF and heparitinase digestion on cell extracts

    PMID:1707883

    Open questions at the time
    • Identity of the 150 kDa HSPG not resolved
    • Whether HSPGs bridge FGF1-FGFR directly or stabilize FGF1 was unknown
  2. 1992 High

    Demonstrating that FGF1 biological activity requires simultaneous engagement of both HSPGs and tyrosine kinase receptors established the dual-receptor signaling paradigm.

    Evidence Chlorate inhibition of sulfation, heparitinase digestion, and heparin rescue in skeletal myoblasts

    PMID:1379245

    Open questions at the time
    • Stoichiometry and structure of the signaling complex were undefined
    • Whether heparin's role was direct bridging versus ligand stabilization remained ambiguous
  3. 2000 High

    Identifying PI3K as essential for FGF1 retrograde nuclear translocation revealed that internalized FGF1 accesses intracrine signaling compartments through an active trafficking mechanism.

    Evidence PI3K chemical inhibitors, dominant-negative PI3K, cell fractionation, and diphtheria toxin fusion tracking

    PMID:10766827

    Open questions at the time
    • PI3K substrate mediating nuclear import not identified
    • Whether nuclear FGF1 has distinct functions from surface-signaled FGF1 was unresolved
  4. 2002 High

    Discovery that FGF1 directly binds and is phosphorylated by CK2, with mitogenic potency correlating with CK2α binding, linked an intracellular kinase to FGF1 functional output.

    Evidence SPR binding kinetics, in vitro kinase assay, and FGF1 mutant–mitogenicity correlation

    PMID:12145206

    Open questions at the time
    • Physiological relevance of CK2-mediated FGF1 phosphorylation in vivo not demonstrated
    • Whether CK2 interaction occurs during nuclear or cytosolic transit unclear
  5. 2003 Medium

    Characterization of FGF1's non-classical, ER/Golgi-independent secretion via a Cu²⁺-dependent multiprotein complex with S100A13 revealed how a leaderless growth factor reaches the extracellular space.

    Evidence Cu²⁺ chelator inhibition, multiprotein complex identification, stress-induced export assays

    PMID:14625381

    Open questions at the time
    • Full reconstitution of export in a cell-free system not achieved
    • Mechanism of membrane translocation remained speculative (molten globule model)
  6. 2005 High

    Reconstitution of 2:2:1 FGF1:FGFR2c:heparin ternary complexes demonstrated that heparin-induced FGF1 dimerization drives receptor assembly and that FGF1 alone has no FGFR2c affinity.

    Evidence Size-exclusion chromatography with defined heparin oligosaccharides correlated with mitogenic assays

    PMID:16219767

    Open questions at the time
    • Whether this stoichiometry applies to all FGFR isoforms was untested
    • Signaling dynamics of the assembled complex not addressed
  7. 2007 High

    Identification of SphK1 as an essential component of the Cu²⁺-dependent FGF1 export complex expanded the non-classical secretion machinery beyond S100A13.

    Evidence SphK1-null cell export failure, cell-free complex formation with copper dependence, rescue by SphK1 overexpression

    PMID:17643421

    Open questions at the time
    • Whether SphK1 enzymatic activity or scaffolding function is required was not dissected
    • Lipid intermediates in export pathway not identified
  8. 2008 High

    Direct binding of FGF1 to integrin αvβ3 and the finding that integrin-binding-defective FGF1 (R50E) fails to stimulate proliferation/migration despite normal FGFR activation established integrin as a required co-signaling partner.

    Evidence Binding assays, R50E mutagenesis, proliferation and migration readouts with intact FGFR/ERK/AKT signaling

    PMID:18441324

    Open questions at the time
    • Integrin-dependent downstream effectors not identified
    • Whether integrin requirement is universal across cell types was untested
  9. 2009 High

    Demonstrating that thermostabilized FGF1 variants compensate for reduced heparin binding reframed heparin's primary role as stabilizing FGF1 against degradation rather than directly mediating FGFR interaction.

    Evidence Systematic FGF1 mutagenesis varying stability and heparin affinity independently, with mitogenic and FGFR activation assays

    PMID:19574212

    Open questions at the time
    • In vivo relevance of stabilization model not tested
    • Whether stabilization role extends to all FGF family members unknown
  10. 2009 High

    Nuclear FGF1 was shown to be required for both neurotrophic activity and p53-dependent apoptosis protection, establishing an intracrine signaling axis distinct from surface receptor activation.

    Evidence ΔNLS FGF1 mutants in PC12 cells with differentiation, survival, and p53 co-immunoprecipitation readouts

    PMID:19765618

    Open questions at the time
    • Whether FGF1–p53 interaction is direct or complex-mediated was not resolved
    • Nuclear FGF1 target genes not identified
  11. 2011 High

    Structural determination of FGF1–FGFR2b and identification of three N-terminal residues conferring pan-FGFR binding explained why FGF1 is the only universal FGFR ligand.

    Evidence 2.1 Å crystal structure and gain-of-function mutagenesis transferring universal binding to FGF2

    PMID:22057274

    Open questions at the time
    • Whether pan-FGFR binding produces identical or isoform-specific downstream signaling was not addressed
  12. 2013 High

    The integrin-binding-defective R50E mutant acting as a dominant-negative inhibitor of angiogenesis and tumor growth demonstrated that disrupting the FGF1–integrin axis is sufficient to block FGF-driven pathological angiogenesis.

    Evidence Tube formation, matrigel plug, CAM assays, aorta ring assay, and tumor xenografts

    PMID:23469107

    Open questions at the time
    • Mechanism of dominant-negative action (competition for integrin vs. FGFR) not fully resolved
    • Therapeutic window and specificity in vivo not characterized
  13. 2014 High

    Identification of nucleolin as the intranuclear partner directing PKCδ phosphorylation and subsequent nuclear export of FGF1 completed the intracrine trafficking cycle: nuclear import → nucleolin binding → phosphorylation → export.

    Evidence SPR, MS identification, nucleolin knockdown, phosphomimetic FGF1 mutants, trafficking assays

    PMID:24595027

    Open questions at the time
    • Whether nucleolin acts as a chaperone or scaffold for PKCδ is unclear
    • Nuclear functions executed before export not defined
  14. 2014 High

    Discovery that FGF1-induced cardiomyocyte cell cycle reentry requires FGFR1–Fn14 co-receptor interaction and synergy with TWEAK identified a mechanism for cardiac regeneration signaling.

    Evidence Reciprocal co-IP, proximity ligation assay, dominant-negative Fn14, cell cycle reentry assays

    PMID:24571920

    Open questions at the time
    • In vivo cardiac regeneration outcome not tested
    • Whether Fn14 interaction is required for other FGF1 functions unknown
  15. 2014 High

    Pharmacological FGF1 delivery achieving insulin sensitization via FGFR1 — separable from mitogenic activity — established FGF1 as a metabolic hormone with therapeutic potential.

    Evidence Recombinant FGF1 in diabetic mice, glucose/insulin clamp, FGFR inhibitors, non-mitogenic FGF1 variants

    PMID:25043058

    Open questions at the time
    • Tissue-specific FGFR1 target mediating metabolic effects not identified at the time
    • Long-term safety of non-mitogenic variants untested
  16. 2015 High

    AHNAK2 was identified as a stress-induced component of the FGF1 export complex that mediates submembrane translocation, expanding the secretion machinery to include cytoskeletal interactions.

    Evidence IP-MS, AHNAK2 depletion reducing FGF1 but not FGF2 export, F-actin fractionation

    PMID:25560297

    Open questions at the time
    • Direct versus indirect AHNAK2–FGF1 interaction not resolved
    • Order of assembly of S100A13/SphK1/AHNAK2 complex undefined
  17. 2015 High

    Genetic evidence in zebrafish that FGF1 mediates ER-stress-induced compensatory β-cell differentiation established FGF1 as an autocrine/paracrine β-cell expansion factor.

    Evidence fgf1 knockout, β-cell-specific rescue, constitutive secretion constructs, ER stress epistasis in zebrafish

    PMID:26420862

    Open questions at the time
    • Whether this mechanism operates in mammalian β-cells not confirmed
    • Downstream transcriptional targets in β-cell progenitors unknown
  18. 2020 High

    Identification of Piezo1 as the mechanosensor releasing FGF1 from adipocytes to drive FGFR1-dependent adipogenesis revealed a mechanotransduction-to-growth-factor secretion axis in adipose tissue.

    Evidence Adipocyte-specific Piezo1 knockout mice on high-fat diet, FGF1 secretion measurement, FGFR1 signaling assays

    PMID:32385276

    Open questions at the time
    • Mechanism of Piezo1-triggered FGF1 release (vesicular vs. non-classical) unknown
    • Whether Piezo1–FGF1 axis operates in non-adipose tissues untested
  19. 2022 High

    Pinpointing PDE4D activation and Ser44 phosphorylation as the mechanism by which FGF1 suppresses adipose lipolysis and hepatic glucose production resolved the anti-diabetic effector pathway and distinguished it from insulin's PDE3B mechanism.

    Evidence PDE4D activity assays, phosphosite identification, cAMP-PKA pathway measurement, comparison with insulin pathway

    PMID:34986332

    Open questions at the time
    • Kinase phosphorylating PDE4D at Ser44 downstream of FGF1–FGFR not identified
    • Whether PDE4D activation is relevant to central (brain) FGF1 glucose-lowering action unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the complete order of assembly and membrane translocation mechanism of the non-classical export complex, the identity of nuclear FGF1 transcriptional targets, and whether the PDE4D-mediated metabolic mechanism extends to CNS-mediated glucose lowering.
  • Full reconstitution of the non-classical secretion complex in vitro not achieved
  • Nuclear FGF1 target genes remain unidentified
  • Relative contributions of peripheral versus central FGF1 metabolic actions not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005576 extracellular region 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1430728 Metabolism 3 R-HSA-9609507 Protein localization 3 R-HSA-1266738 Developmental Biology 2
Partners
AHNAK2FGFR1FGFR2ITGAVITGB3NCLS100A13SPHK1
Complex memberships
FGF1-FGFR-HSPG ternary signaling complexFGF1-S100A13-SphK1-AHNAK2 export complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 FGF1 (aFGF) signaling requires simultaneous binding to both a heparan sulfate proteoglycan (HSPG) and a tyrosine kinase receptor; chlorate inhibition of glycosaminoglycan sulfation abolished FGF1 biological activity in skeletal muscle myoblasts, and this was reversed by heparin or sodium sulfate addition. Chlorate treatment to inhibit glycosaminoglycan sulfation, heparitinase digestion, heparin rescue experiments, FGF binding assays The Journal of cell biology High 1379245
1991 FGF1 (aFGF) binds to a 150 kDa heparan sulfate proteoglycan as a high-affinity receptor; heparitinase digestion before affinity labeling markedly reduced binding, demonstrating that the heparan sulfate glycosaminoglycan moiety is critical for high-affinity FGF1 binding. Affinity labeling with 125I-aFGF, Scatchard analysis, heparitinase digestion, ion exchange chromatography The Journal of biological chemistry High 1707883
2003 FGF1 is exported via a non-classical, ER-Golgi-independent pathway that requires Cu2+-dependent formation of a multiprotein complex containing S100A13 protein, and export involves translocation across the membrane possibly as a 'molten globule'. Biochemical characterization of export pathway, Cu2+ chelator inhibition studies, multiprotein complex identification Journal of cell science Medium 14625381
2005 FGF1 dimerizes cooperatively upon a single heparin saccharide (minimum octasaccharide dp8), and this dimerization drives formation of 2:2:1 FGF1:FGFR2c:heparin ternary signaling complexes; without heparin, FGF1 has no detectable affinity for FGFR2c. Size-exclusion chromatography, mitogenic response assays with heparin oligosaccharides of defined length and sulfation The Journal of biological chemistry High 16219767
2008 FGF1 directly binds integrin αvβ3 (Kd ~1 µM) via an integrin-binding site that overlaps with the heparin-binding site but is distinct from the FGFR-binding site; an FGF1 mutant R50E defective in integrin binding fails to induce DNA synthesis, cell proliferation, migration, and chemotaxis despite normal FGFR1 and FRS2α phosphorylation and AKT/ERK activation. Soluble and cell-surface integrin binding assays, docking simulation, site-directed mutagenesis (R50E), proliferation and migration assays The Journal of biological chemistry High 18441324
2002 FGF1 binds to both the catalytic α-subunit (Kd ~0.4 µM) and regulatory β-subunit (Kd ~1.2 µM) of protein kinase CK2; FGF1 is phosphorylated by CK2 in vitro, and FGF1 enhances autophosphorylation of CK2β; correlation exists between the mitogenic potential of FGF1 mutants and their ability to bind CK2α. Affinity pulldown from cell lysates, surface plasmon resonance, in-cell interaction assay, in vitro kinase assay, FGF1 mutant analysis The EMBO journal High 12145206
2000 Translocation of exogenous FGF1 (aFGF) from the cell surface to the cytosol and nucleus requires phosphatidylinositol 3-kinase (PI3K) activity; inhibition of PI3K by chemical inhibitors or dominant-negative mutant blocked nuclear import of FGF1, and FGF1 fused to diphtheria toxin A-fragment remained in the cytosol upon PI3K inhibition even after artificial membrane translocation. PI3K chemical inhibitors, dominant-negative PI3K expression, cell fractionation, farnesylation reporter assay, diphtheria toxin fusion system The Journal of biological chemistry High 10766827
2009 FGF1 nuclear translocation is required for both its neurotrophic activity (differentiation and serum-free survival) and its protection against p53-dependent apoptosis in PC12 neuronal cells; deletion of the nuclear localization sequence (ΔNLS) abolished nuclear entry and both activities; wild-type FGF1 but not ΔNLS FGF1 interacts with p53. Transfection of NLS-deletion FGF1 mutants, cell viability assays, differentiation assays, co-immunoprecipitation with p53 Biochimica et biophysica acta High 19765618
2009 Increased thermodynamic stability of FGF1 compensates for decreased heparin binding affinity in FGFR activation, DNA synthesis induction, and cell proliferation; the main role of heparin in FGF1 signaling is to protect the naturally unstable protein from heat and proteolytic degradation, not to directly mediate FGF1-FGFR interaction. FGF1 variants with reduced heparin affinity and stabilizing mutations, biophysical characterization, DNA synthesis assays, cell proliferation assays, membrane translocation assays The Journal of biological chemistry High 19574212
2011 The N-terminal region of FGF1 (residues Phe-16, Asn-22, Tyr-23) confers plasticity in interactions with both 'b' and 'c' FGFR splice isoforms, making FGF1 a universal FGFR ligand; substitution of these three residues into FGF2 enabled the FGF2 triple mutant to bind and activate FGFR2b. Crystal structure of FGF1-FGFR2b complex at 2.1 Å, mutagenesis of FGF N-terminal residues, FGFR binding and activation assays The Journal of biological chemistry High 22057274
2013 The integrin-binding defective FGF1 mutant R50E acts as a dominant-negative inhibitor of FGF signaling; R50E suppresses FGF1-induced migration and tube formation of endothelial cells, angiogenesis in matrigel plug and CAM assays, and tumor growth in vivo, and also suppresses FGF2-induced angiogenesis. In vitro tube formation assay, matrigel plug assay, chick embryo CAM assay, aorta ring assay, in vivo tumor xenograft PloS one High 23469107
2014 Nucleolin directly interacts with FGF1 (confirmed by surface plasmon resonance); this interaction is required for intranuclear phosphorylation of FGF1 by PKCδ and for subsequent nuclear export of FGF1; FGF1 residues within the heparin-binding site mediate nucleolin binding. Affinity pulldown with mass spectrometry, surface plasmon resonance, nucleolin knockdown, FGF1 mutants with reduced nucleolin binding, phosphomimetic FGF1 mutants, intracellular trafficking assays PloS one High 24595027
2014 FGF1-induced cardiomyocyte cell cycle reentry depends on interaction between FGFR-1 and Fn14 (TNF receptor superfamily member); FGF1 and TWEAK synergistically activate cardiomyocyte cell cycle via PI3K/Akt signaling; endogenous FGFR-1 and Fn14 interact and their interaction is enhanced by ligand stimulation. Co-immunoprecipitation, proximity ligation assay, Fn14 inhibition, dominant-negative experiments, FGFR-1 isoform overexpression, cell cycle reentry assays FASEB journal High 24571920
2014 Chronic pharmacological delivery of recombinant FGF1 increases insulin-dependent glucose uptake in skeletal muscle, suppresses hepatic glucose production, and achieves whole-body insulin sensitization; the glucose-lowering activity is mediated predominantly via FGFR1 signaling and can be dissociated from FGF1's mitogenic activity. Recombinant FGF1 delivery to diabetic mice, glucose and insulin clamp studies, tissue-specific glucose uptake measurements, FGFR inhibitor experiments, non-mitogenic FGF1 variants Nature High 25043058
2007 Sphingosine kinase 1 (SphK1) is a critical component of the copper-dependent FGF1 non-classical export pathway; SphK1 forms a complex with FGF1 in a cell-free system in a copper-dependent manner, SphK1-null cells fail to release FGF1 under stress, and SphK1 overexpression rescues FGF1 release from copper chelator inhibition. SphK1-null cell studies, heat shock-induced export assays, cell-free complex formation, copper chelator rescue experiments, co-expression studies Experimental cell research High 17643421
2015 AHNAK2 participates in the stress-induced non-classical FGF1 secretion pathway; heat shock induces association of FGF1 with AHNAK2 and their co-translocation to the cytoskeletal/F-actin-rich submembrane fraction; AHNAK2 depletion drastically decreases stress-induced FGF1 export without affecting spontaneous FGF2 export. Immunoprecipitation-mass spectrometry, AHNAK2 depletion, co-localization by immunofluorescence, cell fractionation, FGF1 export assays Journal of cellular biochemistry High 25560297
2016 Importin α1 (KPNA2) is localized to the cancer cell surface via interaction with heparan sulfate and directly binds FGF1 (a cNLS-containing growth factor); exogenous importin α1 enhances ERK1/2 activation in FGF1-stimulated cancer cells, and anti-importin α1 antibody suppresses FGF1-importin α1 complex formation, ERK1/2 activation, and cancer cell growth. Cell surface localization studies, co-immunoprecipitation, heparan sulfate binding assays, ERK1/2 phosphorylation assays, antibody inhibition experiments Scientific reports Medium 26887791
2017 FGF1 nuclear translocation (intracrine pathway) protects neuroblastoma SH-SY5Y cells against p53-dependent apoptosis; the C-terminal domain and phosphorylation of FGF1 (Ser130) regulate this intracrine anti-apoptotic activity, as shown by FGF1 mutants K132E, S130A (phospho-null), and S130D (phosphomimetic). FGF1 mutant overexpression (K132E, S130A, S130D), recombinant FGF1 addition, apoptosis assays (mitochondrial pathway markers), comparison of intracellular vs. extracellular FGF1 activity Cell death & disease Medium 29048426
2018 Brain intracerebroventricular FGF1 injection induces remission of hyperglycemia in diabetic rodents through insulin-independent glucose clearance; the mechanism involves increased hepatic glucokinase gene expression and activity (~2-fold), stimulating hepatic glucose uptake. Intracerebroventricular FGF1 injection, glucose-induced insulin secretion assays, insulin sensitivity tests, hepatic glucokinase activity assays, gene expression measurement Diabetes Medium 30523024
2022 FGF1 acutely lowers hepatic glucose production by suppressing adipose lipolysis; mechanistically, FGF1 inhibits the cAMP-PKA axis by activating phosphodiesterase 4D (PDE4D), and Ser44 is identified as an FGF1-induced regulatory phosphorylation site in PDE4D; this is mechanistically distinct from insulin's action via PDE3B. Adipose lipolysis assays, cAMP-PKA measurement, PDE4D activity assays, phosphorylation site identification, FGF1 and insulin pathway comparison, feed-fast cycle studies Cell metabolism High 34986332
2019 In the downstream regulation of FGF1-induced signaling, both p38 kinase and Erk1/2 can phosphorylate FRS2 (a major FGFR signaling mediator); simultaneous inhibition of both Erk1/2 and p38 leads to prolonged FGFR1 and FRS2 tyrosine phosphorylation and sustained signaling, revealing a crosstalk between these kinases in negative feedback. Selective kinase inhibitors, anisomycin activation of p38, FRS2 phosphorylation pattern analysis by western blot, FGFR1 phosphorylation assays in NIH3T3 and U2OS cells stably expressing FGFR1 International journal of molecular sciences Medium 31013829
2009 SH2B1β enhances FGF1-induced neurite outgrowth in PC12 cells through the MEK-ERK1/2-STAT3(S727)-Egr1 pathway; SH2B1β prolongs FGF1-induced MEK-ERK1/2 and PI3K-AKT signaling; FGF1 induces STAT3 phosphorylation at serine 727 in PC12 cells, and MEK-ERK1/2 is required for this phosphorylation and for Egr1 expression. SH2B1β overexpression, pathway inhibitor assays, STAT3 phosphorylation assays, Egr1 expression measurement, neurite outgrowth quantification Cellular signalling Medium 19249349
2020 In adipose tissue, Piezo1 (mechanosensitive channel) in mature adipocytes mediates diet-induced adipogenesis by releasing FGF1 upon opening; released FGF1 induces adipocyte precursor differentiation through activation of FGF receptor 1; adipocyte-specific Piezo1 knockout mice on high-fat diet showed defective preadipocyte differentiation. Adipocyte-specific Piezo1 knockout mice, high-fat diet challenge, FGF1 secretion measurement, FGFR1 signaling assays, adipogenesis assays Nature communications High 32385276
2017 Following associative learning, CRTC1 translocates from synapse to nucleus where it regulates Fgf1b transcription; strong training replaces CBP with KAT5 in the CRTC1/CREB complex at the Fgf1b promoter in a CRTC1-dependent but CREB-phosphorylation-independent manner, leading to long-lasting Fgf1b transcription and memory enhancement. Chromatin immunoprecipitation, nuclear CRTC1 translocation tracking, co-immunoprecipitation of chromatin remodeling complexes, fear conditioning learning paradigms, promoter activity assays Cell reports Medium 28076781
2010 The transcription factor RFX1 directly binds 18-bp cis-elements (-484 to -467) of the FGF1 1B promoter and negatively regulates FGF1 expression; RFX1 overexpression down-regulates FGF-1B mRNA and reduces neurosphere formation in glioblastoma cells, while RFX1 knockdown has opposite effects. Yeast one-hybrid assay, EMSA, chromatin immunoprecipitation, gain- and loss-of-function assays, neurosphere assays The Journal of biological chemistry High 20189986
2015 FGF1 mediates overnutrition-induced compensatory β-cell differentiation in zebrafish; fgf1 inactivation abolished compensatory β-cell differentiation; FGF1 expression solely in β-cells rescued compensatory response in fgf1-/- animals; constitutive FGF1 secretion increased β-cell number; ER stress acts upstream of FGF1 release from β-cells. Zebrafish small molecule screen, fgf1 genetic inactivation, β-cell-specific FGF1 rescue, constitutive secretion constructs, ER stress manipulation Diabetes High 26420862

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America 300 17032753
1992 Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on cellular heparan sulfate. The Journal of cell biology 223 1379245
2014 Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature 206 25043058
2003 The non-classical export routes: FGF1 and IL-1alpha point the way. Journal of cell science 163 14625381
2016 Comparative Study of Heparin-Poloxamer Hydrogel Modified bFGF and aFGF for in Vivo Wound Healing Efficiency. ACS applied materials & interfaces 140 27384134
2020 Adipocyte Piezo1 mediates obesogenic adipogenesis through the FGF1/FGFR1 signaling pathway in mice. Nature communications 120 32385276
2008 Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1 signaling. The Journal of biological chemistry 117 18441324
2015 Increased FGF1-FGFRc expression in idiopathic pulmonary fibrosis. Respiratory research 108 26138239
2017 TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 99 29268138
2021 FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression. Signal transduction and targeted therapy 98 33762571
1997 Transfection with aFGF cDNA improves wound healing. The Journal of investigative dermatology 87 9036931
2022 FGF1 and insulin control lipolysis by convergent pathways. Cell metabolism 85 34986332
2019 FGF1ΔHBS ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation. Cell death & disease 82 31189876
2022 FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress. Molecular medicine (Cambridge, Mass.) 81 35764933
1991 Identification of heparan sulfate proteoglycan as a high affinity receptor for acidic fibroblast growth factor (aFGF) in a parathyroid cell line. The Journal of biological chemistry 81 1707883
2014 WNT7A/β-catenin signaling induces FGF1 and influences sensitivity to niclosamide in ovarian cancer. Oncogene 79 25174399
1989 Immunological study of acidic fibroblast growth factor (aFGF) distribution in the eye. Journal of cellular biochemistry 79 2654149
2002 Peripheral nerve grafts and aFGF restore partial hindlimb function in adult paraplegic rats. Journal of neurotrauma 76 12427329
2005 Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes. The Journal of biological chemistry 60 16219767
2021 MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis. International journal of biological sciences 57 33994863
2010 Altered splicing of FGFR1 is associated with high tumor grade and stage and leads to increased sensitivity to FGF1 in bladder cancer. The American journal of pathology 57 20889570
1994 Up-regulation of aFGF expression in quiescent cells is related to cell survival. Journal of cellular physiology 57 7510293
2022 MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling. Cardiovascular research 56 34358309
2009 Increased protein stability of FGF1 can compensate for its reduced affinity for heparin. The Journal of biological chemistry 55 19574212
2017 CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene. Cell reports 54 28076781
2000 TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma. International journal of oncology 53 10938383
2002 Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity. The EMBO journal 52 12145206
1999 aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8. The Journal of pathology 49 10629559
1995 bFGF and aFGF induce membrane ruffling in breast cancer cells but not in normal breast epithelial cells: FGFR-4 involvement. The Biochemical journal 49 7534069
2018 Peripheral Mechanisms Mediating the Sustained Antidiabetic Action of FGF1 in the Brain. Diabetes 48 30523024
2017 Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model. Stem cell reviews and reports 46 28795363
2013 A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis. PloS one 45 23469107
1997 Expression of FGF-1 and FGF-2 mRNA during lens morphogenesis, differentiation and growth. Current eye research 45 9088738
2021 MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1. Experimental cell research 43 33957117
2009 FGF1 nuclear translocation is required for both its neurotrophic activity and its p53-dependent apoptosis protection. Biochimica et biophysica acta 43 19765618
1995 FGF-1 in normal and regenerating kidney: expression in mononuclear, interstitial, and regenerating epithelial cells. The American journal of physiology 42 7503231
2005 FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis. Journal of reproductive immunology 41 16165218
1993 Cloning of two novel forms of human acidic fibroblast growth factor (aFGF) mRNA. Nucleic acids research 41 7680120
2011 Plasticity in interactions of fibroblast growth factor 1 (FGF1) N terminus with FGF receptors underlies promiscuity of FGF1. The Journal of biological chemistry 40 22057274
2010 Immunohistochemical study of the growth factors, aFGF, bFGF, PDGF-AB, VEGF-A and its receptor (Flk-1) during arteriogenesis. Molecular and cellular biochemistry 40 20559689
2022 Myeloid-derived suppressor cells promote tumor growth and sorafenib resistance by inducing FGF1 upregulation and fibrosis. Neoplasia (New York, N.Y.) 39 35378464
2009 SH2B1beta enhances fibroblast growth factor 1 (FGF1)-induced neurite outgrowth through MEK-ERK1/2-STAT3-Egr1 pathway. Cellular signalling 39 19249349
1992 Endogenous aFGF expression and cellular changes after a demyelinating lesion in the spinal cord of adult normal mice: immunohistochemical study. Journal of neuroscience research 39 1280690
2011 Variation in FGF1, FOXE1, and TIMP2 genes is associated with nonsyndromic cleft lip with or without cleft palate. Birth defects research. Part A, Clinical and molecular teratology 38 21462296
1998 Effects of aFGF, bFGF, TGFbeta1 and IGF-I on odontoblast differentiation in vitro. European journal of oral sciences 38 9541212
2020 MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A. Frontiers in pharmacology 36 32210827
2024 The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation. Cells 35 38474378
2017 FGF1 and IGF1-conditioned 3D culture system promoted the amplification and cancer stemness of lung cancer cells. Biomaterials 35 29017078
2016 Cell surface localization of importin α1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling. Scientific reports 35 26887791
2010 Regulation of FGF1 gene promoter through transcription factor RFX1. The Journal of biological chemistry 35 20189986
2017 lncRNA-Map2k4 sequesters miR-199a to promote FGF1 expression and spinal cord neuron growth. Biochemical and biophysical research communications 34 28655615
2016 Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity. Molecular cancer research : MCR 34 27353029
2015 FGF1-FGFR1 axis promotes tongue squamous cell carcinoma (TSCC) metastasis through epithelial-mesenchymal transition (EMT). Biochemical and biophysical research communications 34 26362179
1996 Expression of FGF1 and FGFR1 in human melanoma tissues. Melanoma research 34 8819125
2000 Requirement of phosphatidylinositol 3-kinase activity for translocation of exogenous aFGF to the cytosol and nucleus. The Journal of biological chemistry 33 10766827
1987 Biomaterial pretreatment with ECGF to augment endothelial cell proliferation. Journal of vascular surgery 33 2950245
2001 Endothelial cell growth factor (ECGF) enmeshed with fibrin matrix enhances proliferation of EC in vitro. Biomaterials 32 11545311
2000 Enkephalin and aFGF are differentially regulated in rat spinal motoneurons after chemodenervation with botulinum toxin. Experimental neurology 32 10683301
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1999 Expression of platelet-derived endothelial cell growth factor (PD-ECGF) related to angiogenesis in ovarian endometriosis. The Journal of clinical endocrinology and metabolism 28 9920107
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2014 Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library. Biochemical and biophysical research communications 27 24530908
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2018 Mast cells and immunoexpression of FGF-1 and Ki-67 in rat subcutaneous tissue following the implantation of Biodentine and MTA Angelus. International endodontic journal 20 29975794
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