Functional interaction of VEGF-C and VEGF-D with neuropilin receptors

Terhi Kärpänen, Caroline A Heckman, Salla Keskitalo, Michael Jeltsch, Hanna Ollila, Gera Neufeld, Luca Tamagnone, Kari Alitalo

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Lymphatic vascular development is regulated by vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature.
    Original languageEnglish
    JournalFASEB Journal
    Volume20
    Issue number9
    Pages (from-to)1462.1472
    Number of pages1
    ISSN0892-6638
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Cite this

    Kärpänen, Terhi ; Heckman, Caroline A ; Keskitalo, Salla ; Jeltsch, Michael ; Ollila, Hanna ; Neufeld, Gera ; Tamagnone, Luca ; Alitalo, Kari. / Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. In: FASEB Journal. 2006 ; Vol. 20, No. 9. pp. 1462.1472.
    @article{bda4fa6aa13c4479af674b0bcabbc115,
    title = "Functional interaction of VEGF-C and VEGF-D with neuropilin receptors",
    abstract = "Lymphatic vascular development is regulated by vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature.",
    author = "Terhi K{\"a}rp{\"a}nen and Heckman, {Caroline A} and Salla Keskitalo and Michael Jeltsch and Hanna Ollila and Gera Neufeld and Luca Tamagnone and Kari Alitalo",
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    Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. / Kärpänen, Terhi; Heckman, Caroline A; Keskitalo, Salla; Jeltsch, Michael; Ollila, Hanna; Neufeld, Gera; Tamagnone, Luca; Alitalo, Kari.

    In: FASEB Journal, Vol. 20, No. 9, 2006, p. 1462.1472.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Functional interaction of VEGF-C and VEGF-D with neuropilin receptors

    AU - Kärpänen, Terhi

    AU - Heckman, Caroline A

    AU - Keskitalo, Salla

    AU - Jeltsch, Michael

    AU - Ollila, Hanna

    AU - Neufeld, Gera

    AU - Tamagnone, Luca

    AU - Alitalo, Kari

    PY - 2006

    Y1 - 2006

    N2 - Lymphatic vascular development is regulated by vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature.

    AB - Lymphatic vascular development is regulated by vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature.

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    DO - 10.1096/fj-05-5646com

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