دورية أكاديمية
Ligand bias underlies differential signaling of multiple FGFs via FGFR1.
العنوان: | Ligand bias underlies differential signaling of multiple FGFs via FGFR1. |
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المؤلفون: | Karl K; Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, United States., Del Piccolo N; Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, United States., Light T; Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, United States., Roy T; Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, United States., Dudeja P; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Institute of Animal Physiology and Genetics of the CAS, Brno, Czech Republic., Ursachi VC; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Fafilek B; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Institute of Animal Physiology and Genetics of the CAS, Brno, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Krejci P; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Institute of Animal Physiology and Genetics of the CAS, Brno, Czech Republic.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic., Hristova K; Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, United States. |
المصدر: | ELife [Elife] 2024 Apr 03; Vol. 12. Date of Electronic Publication: 2024 Apr 03. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
مواضيع طبية MeSH: | Signal Transduction* , Fibroblast Growth Factors*, Female ; Pregnancy ; Humans ; Ligands ; Phosphorylation ; Bias ; Receptor, Fibroblast Growth Factor, Type 1/genetics |
مستخلص: | The differential signaling of multiple FGF ligands through a single fibroblast growth factor (FGF) receptor (FGFR) plays an important role in embryonic development. Here, we use quantitative biophysical tools to uncover the mechanism behind differences in FGFR1c signaling in response to FGF4, FGF8, and FGF9, a process which is relevant for limb bud outgrowth. We find that FGF8 preferentially induces FRS2 phosphorylation and extracellular matrix loss, while FGF4 and FGF9 preferentially induce FGFR1c phosphorylation and cell growth arrest. Thus, we demonstrate that FGF8 is a biased FGFR1c ligand, as compared to FGF4 and FGF9. Förster resonance energy transfer experiments reveal a correlation between biased signaling and the conformation of the FGFR1c transmembrane domain dimer. Our findings expand the mechanistic understanding of FGF signaling during development and bring the poorly understood concept of receptor tyrosine kinase ligand bias into the spotlight. Competing Interests: KK, ND, TL, TR, PD, VU, BF, PK, KH No competing interests declared (© 2023, Karl et al.) |
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معلومات مُعتمدة: | R01 GM068619 United States GM NIGMS NIH HHS; GM068619 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: FGFR; biased signaling; molecular biophysics; none; signal transduction; structural biology |
المشرفين على المادة: | 0 (Ligands) 62031-54-3 (Fibroblast Growth Factors) EC 2.7.10.1 (FGFR1 protein, human) EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) |
تواريخ الأحداث: | Date Created: 20240403 Date Completed: 20240404 Latest Revision: 20240531 |
رمز التحديث: | 20240531 |
مُعرف محوري في PubMed: | PMC10990489 |
DOI: | 10.7554/eLife.88144 |
PMID: | 38568193 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2050-084X |
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DOI: | 10.7554/eLife.88144 |