{
  "abstract": "Fibroblast growth factor receptors 1 and 4 (FGFR1/4) regulate diverse cellular processes, including proliferation, differentiation, and metabolic homeostasis. Although ligand-dependent FGFR signaling has been extensively characterized, the signaling properties of these receptors in their ligand-independent state remain poorly understood. Here, we investigated the intrinsic signaling outputs of FGFR1 and FGFR4 in the absence of ligands using quantitative immunoblotting and electrophysiological analyses. Overexpression of FGFR1 or FGFR4 alone robustly increased the phosphorylation of phospholipase Cγ (PLCγ) and extracellular signal-regulated kinase 1/2 (ERK1/2), whereas activation of the PI3K–Akt pathway was minimal. Strikingly, co-expression of the co-receptor βKlotho acted as a molecular switch, selectively suppressing FGFR-driven PLCγ phosphorylation while preserving ERK1/2 signaling. Functionally, this βKlotho-dependent attenuation of PLCγ signaling markedly reduced the sustained TRPC6-mediated currents observed in βKlotho-deficient cells, linking constitutive FGFR–PLCγ coupling to aberrant Ca²+ influx. Together, our findings identify βKlotho as a specialized signaling filter that safeguards FGFR signaling fidelity by uncoupling deleterious PLCγ–TRPC6 signaling while maintaining canonical MAPK output. These results reveal a previously unrecognized ligand-independent role of βKlotho in reconfiguring the FGFR signaling architecture.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology, Yonsei University Wonju College of Medicine Wonju 26426 Korea",
    "Department of Global Medical Science, Yonsei University Wonju College of Medicine Wonju 26426 Korea",
    "Organelle Medicine Research Center, Yonsei University Wonju College of Medicine Wonju 26426 Korea",
    "Institute of Mitochondrial Medicine, Yonsei University Wonju College of Medicine Wonju 26426 Korea",
    "Department of Medicine, Yonsei University Wonju College of Medicine Wonju 26426 Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Bao T. N. Dang"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Phan Anh Nguyen"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Subo Lee"
    },
    {
      "affs": [
        0,
        2,
        3,
        4
      ],
      "name": "Hyungmin Jeong"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Seung-Kuy Cha",
      "orcid": "0000-0003-3201-7950"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8agj24fj289ec.bib",
  "cited_by": 0,
  "doi": "10.4196/kjpp.26.060",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13728267/",
  "id": "8agj24fj289ec",
  "issns": [
    "1226-4512",
    "2093-3827"
  ],
  "landing_url": "https://doi.org/10.4196/kjpp.26.060",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2727|Parathyroid Disorders and Treatments"
    ]
  ],
  "openalex": "W7216157619",
  "pdf_url": "https://www.kjpp.net/journal/download_pdf.php?doi=10.4196/kjpp.26.060",
  "pmcid": "PMC13728267",
  "pmid": "42825310",
  "published": "2026-11-01",
  "publisher": "Korean Physiological Society and Korean Society of Pharmacology",
  "ris": "https://research.draconitic.com/paper/8agj24fj289ec.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:59Z",
      "native_id": "PMC13728267",
      "source": "pmc",
      "url": "https://doi.org/10.4196/kjpp.26.060"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Parathyroid Disorders and Treatments",
      "subfield": "general"
    }
  ],
  "title": "βKlotho filters ligand-independent FGFR1/4-PLCγ signaling to prevent aberrant constitutive Ca2+ entry",
  "title_text": "βKlotho filters ligand-independent FGFR1/4-PLCγ signaling to prevent aberrant constitutive Ca2+ entry",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:17Z",
  "url": "https://research.draconitic.com/paper/8agj24fj289ec",
  "venue": "The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology",
  "versions": []
}