ArticleThe Journal of biological chemistry2012
Plasticity in interactions of fibroblast growth factor 1 (FGF1) N terminus with FGF receptors underlies promiscuity of FGF1.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
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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
31 citing papers in PubMed, 47 citations in OpenAlex.
- FGF1-FGFR2 axis regulated by nuclear receptor RORγ represents an effective strategy in intrahepatic cholangiocarcinoma.Cell death discovery · 2025Article
- N-terminal helix formation and dimer-monomer transition of FGF10 in specific recognition of FGFR2b.The FEBS journal · 2025Article
- FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control.Cells · 2025Review
- Pathology and Therapeutic Significance of Fibroblast Growth Factors.Targets (Basel) · 2025Article
- Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance.Biomolecules · 2024Review
- FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.Cellular and molecular life sciences : CMLS · 2024Article
- Deciphering the etiology of undiagnosed ocular anomalies along with systemic alterations in pediatric patients through whole exome sequencing.Scientific reports · 2024Article
- A homozygous missense mutation in the fibroblast growth factor 5 gene is associated with the long-hair trait in Angora rabbits.BMC genomics · 2023Article
- Isoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein.Cell reports · 2022Article
- Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer.Nature cancer · 2022Article
- FGFR4: A promising therapeutic target for breast cancer and other solid tumors.Pharmacology & therapeutics · 2020Review
- Polarizing receptor activation dissociates fibroblast growth factor 2 mediated inhibition of myelination from its neuroprotective potential.Acta neuropathologica communications · 2019Article
- Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish.Biology open · 2019Article
- Resistance to visceral obesity is associated with increased locomotion in mice expressing an endothelial cell-specific fibroblast growth factor 1 transgene.Physiological reports · 2019Article
- Paracrine Fibroblast Growth Factor 1 Functions as Potent Therapeutic Agent for Intrahepatic Cholestasis by Downregulating Synthesis of Bile Acid.Frontiers in pharmacology · 2019Article
- Structural Biology of the FGF7 Subfamily.Frontiers in genetics · 2019Review
- Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting.Biochemical Society transactions · 2018Review
- Probing the role of proline -135 on the structure, stability, and cell proliferation activity of human acidic fibroblast growth factor.Archives of biochemistry and biophysics · 2018Article
- Investigating the dynamics and polyanion binding sites of fibroblast growth factor-1 using hydrogen-deuterium exchange mass spectrometry.Protein science : a publication of the Protein Society · 2018Article
- Effect of extension of the heparin binding pocket on the structure, stability, and cell proliferation activity of the human acidic fibroblast growth factor.Biochemistry and biophysics reports · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tissue-specific alternative splicing in the second half of Ig-like domain 3 (D3) of fibroblast growth factor receptors 1-3 (FGFR1 to -3) generates epithelial FGFR1b-FGFR3b and mesenchymal FGFR1c-FGFR3c splice isoforms. This splicing event establishes a selectivity filter to restrict the ligand binding specificity of FGFRb and FGFRc isoforms to mesenchymally and epithelially derived fibroblast growth factors (FGFs), respectively. FGF1 is termed the "universal FGFR ligand" because it overrides this specificity barrier. To elucidate the molecular basis for FGF1 cross-reactivity with the "b" and "c" splice isoforms of FGFRs, we determined the first crystal structure of FGF1 in complex with an FGFRb isoform, FGFR2b, at 2.1 Å resolution. Comparison of the FGF1-FGFR2b structure with the three previously published FGF1-FGFRc structures reveals that plasticity in the interactions of the N-terminal region of FGF1 with FGFR D3 is the main determinant of FGF1 cross-reactivity with both isoforms of FGFRs. In support of our structural data, we demonstrate that substitution of three N-terminal residues (Gly-19, His-25, and Phe-26) of FGF2 (a ligand that does not bind FGFR2b) for the corresponding residues of FGF1 (Phe-16, Asn-22, and Tyr-23) enables the FGF2 triple mutant to bind and activate FGFR2b. These findings taken together with our previous structural data on receptor binding specificity of FGF2, FGF8, and FGF10 conclusively show that sequence divergence at the N termini of FGFs is the primary regulator of the receptor binding specificity and promiscuity of FGFs.
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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.