{
  "abstract": "The molecular mechanisms that drive (lymph-)angiogenesis are crucial to understanding diseases, such as lymphedema, that are caused due to malformations of the lymphatic vasculature. Recently, an interaction between the secreted protein Svep1, a key regulator in lymphangiogenesis, and the transmembrane receptor Tie1 was shown in zebrafish, humans, and mice. Here, guided by in silico AlphaFold-multimer structure predictions of SVEP1 complexes, we assert with protein binding studies that the human CCP20 domain is the primary binding site for TIE1. We further demonstrate that SVEP1 mediates strong binding of ANG2 and TIE1, and that combined stimulation of hdLECs with SVEP1 and ANG2 leads to phosphorylation of TIE1. TIE1 activation by SVEP1 and ANG2 enables downstream signaling and, in turn, potentiates nuclear exclusion of FOXO1 and phosphorylation of AKT compared to SVEP1 or ANG2 alone. We present a model in which ANG1/2 dimers bind to both SVEP1 and TIE1, resulting in the recruitment of multiple TIE1 receptor molecules to a multimeric complex at the cell membrane, potentially amplifying its signaling capacity.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, University of Münster, Münster, Germany",
    "Department of Chemistry, University of Manitoba, Winnipeg, Canada",
    "Colzyx AB, Lund, Sweden",
    "Institute for Dental Research and Oral Musculoskeletal Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany",
    "ħ bioconsulting llc, Stillwater, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Katharina Uphoff"
    },
    {
      "affs": [
        0
      ],
      "name": "Melina Hußmann",
      "orcid": "0000-0003-4798-7503"
    },
    {
      "affs": [
        1
      ],
      "name": "Oliver Peters",
      "orcid": "0000-0001-8671-6955"
    },
    {
      "affs": [
        2
      ],
      "name": "Matthias Mörgelin",
      "orcid": "0000-0002-6212-6990"
    },
    {
      "affs": [
        3
      ],
      "name": "Fabian Metzen",
      "orcid": "0000-0002-5248-8218"
    },
    {
      "affs": [
        3
      ],
      "name": "Wolfgang MJ Obermann"
    },
    {
      "affs": [
        4
      ],
      "name": "Fernando J Bazan"
    },
    {
      "affs": [
        1
      ],
      "name": "Jörg Stetefeld",
      "orcid": "0000-0003-1478-3248"
    },
    {
      "affs": [
        3
      ],
      "name": "Manuel Koch",
      "orcid": "0000-0002-2962-7814"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefan Schulte-Merker",
      "orcid": "0000-0003-3617-8807"
    },
    {
      "affs": [
        0
      ],
      "name": "Dörte Schulte-Ostermann",
      "orcid": "0000-0003-2375-9258"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9zd3mjkj35jd9.bib",
  "cited_by": 2,
  "doi": "10.7554/elife.106338",
  "fulltext_url": "https://elifesciences.org/articles/106338",
  "id": "9zd3mjkj35jd9",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://elifesciences.org/articles/106338",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "elife",
      "cell-biology"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2730|Lymphatic System and Diseases"
    ]
  ],
  "openalex": "W4410858629",
  "pdf_url": "https://cdn.elifesciences.org/articles/106338/elife-106338-v1.pdf",
  "pmcid": "PMC13722417",
  "pmid": "42960837",
  "published": "2026-10-30",
  "publisher": "eLife Sciences Publications",
  "ris": "https://research.draconitic.com/paper/9zd3mjkj35jd9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:25Z",
      "native_id": "106338",
      "source": "elife",
      "url": "https://elifesciences.org/articles/106338"
    },
    {
      "first_seen": "2026-11-01T00:20:50Z",
      "native_id": "MED:42960837",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960837"
    },
    {
      "first_seen": "2026-11-03T12:22:55Z",
      "native_id": "PMC13722417",
      "source": "pmc",
      "url": "https://doi.org/10.7554/elife.106338"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "elife:cell-biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "SVEP1 enables efficient binding of angiopoietin-2 to the TIE1 receptor, allowing receptor phosphorylation and downstream signaling",
  "title_text": "SVEP1 enables efficient binding of angiopoietin-2 to the TIE1 receptor, allowing receptor phosphorylation and downstream signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:55Z",
  "url": "https://research.draconitic.com/paper/9zd3mjkj35jd9",
  "venue": "eLife",
  "versions": []
}