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Ligand bias underlies differential signaling of multiple FGFs via FGFR1

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F24%3A00585091" target="_blank" >RIV/67985904:_____/24:00585091 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14110/24:00136112 RIV/00159816:_____/24:00081460

  • Result on the web

    <a href="https://elifesciences.org/articles/88144" target="_blank" >https://elifesciences.org/articles/88144</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.7554/eLife.88144" target="_blank" >10.7554/eLife.88144</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Ligand bias underlies differential signaling of multiple FGFs via FGFR1

  • Original language description

    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. Forster 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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10605 - Developmental biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    eLife

  • ISSN

    2050-084X

  • e-ISSN

    2050-084X

  • Volume of the periodical

    12

  • Issue of the periodical within the volume

    Apr 3

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    28

  • Pages from-to

    RP88144

  • UT code for WoS article

    001196755600001

  • EID of the result in the Scopus database