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• W1486302655 abstract "The endocrine fibroblast growth factor 21 (FGF21) requires both fibroblast growth factor receptor (FGFR) and β-Klotho for signaling. In this study, we sought to understand the inter-molecular physical interactions in the FGF21/FGFR/β-Klotho complex by deleting key regions in FGFR1c or FGF21. Deletion of the D1 and the D1-D2 linker (the D1/linker region) from FGFR1c led to β-Klotho-independent receptor activation by FGF21, suggesting that there may be a direct interaction between FGF21 and the D1/linker region-deficient FGFR1c. Consistent with this, the extracellular portion of FGFR1c lacking the D1/linker region blocked FGF21 action in a reporter assay, presumably by binding to and sequestering FGF21 from acting on cell surface receptor complex. In addition, the D1/linker region-deficient FGFR1c had enhanced interaction with β-Klotho. Further, we demonstrated that deletion of the D1/linker region enhanced the formation of the FGF21/β-Klotho/FGFR1c ternary complex in both Biacore and asymmetrical flow field flow fractionation studies. Finally, we found that the N-terminus of FGF21 is involved in the interaction with FGFR1c and FGF21/β-Klotho/FGFR1c ternary complex formation. Taken together, our data suggest that the D1/linker region regulates both the FGF21/FGFR1c and FGFR1c/β-Klotho interaction, and a direct interaction of FGF21 with FGFR1c may be an important step in receptor-mediated FGF21 signaling." @default.
• W1486302655 created "2016-06-24" @default.
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• W1486302655 date "2012-02-01" @default.
• W1486302655 modified "2023-10-14" @default.
• W1486302655 title "Understanding the Physical Interactions in the FGF21/FGFR/β-Klotho Complex: Structural Requirements and Implications in FGF21 Signaling" @default.
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• W1486302655 doi "https://doi.org/10.1111/j.1747-0285.2012.01325.x" @default.
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