Academic Journal
uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis.
| العنوان: | uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis. |
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| المؤلفون: | Durré, Tania, Morfoisse, Florent, Erpicum, Charlotte, Ebroin, Marie, Blacher, Silvia, García-Caballero, Melissa, Deroanne, Christophe, Louis, Thomas, Balsat, Cédric, Van de Velde, Maureen, Kaijalainen, Seppo, Kridelka, Frederic, Engelholm, Lars, Struman, Ingrid, Alitalo, Kari, Behrendt, Niels, Paupert, Jenny, Noël, Agnès |
| المصدر: | Nature communications, 9 (1 |
| سنة النشر: | 2018 |
| المجموعة: | DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: | Sciences bio-médicales et agricoles, Cancérologie, Animals, Cell Line, Tumor, Dimerization, Endothelial Cells -- metabolism -- pathology, Female, Humans, Lymphangiogenesis, Lymphatic Vessels -- metabolism -- pathology, Male, Membrane Glycoproteins -- genetics -- metabolism, Mice, Receptors, Cell Surface -- genetics -- metabolism, Signal Transduction, Vascular Endothelial Growth Factor C -- metabolism, Vascular Endothelial Growth Factor Receptor-2 -- chemistry -- genetics -- metabolism, Vascular Endothelial Growth Factor Receptor-3 -- chemistry -- genetics -- metabolism |
| الوصف: | The development of new lymphatic vessels occurs in many cancerous and inflammatory diseases through the binding of VEGF-C to its receptors, VEGFR-2 and VEGFR-3. The regulation of VEGFR-2/VEGFR-3 heterodimerisation and its downstream signaling in lymphatic endothelial cells (LECs) remain poorly understood. Here, we identify the endocytic receptor, uPARAP, as a partner of VEGFR-2 and VEGFR-3 that regulates their heterodimerisation. Genetic ablation of uPARAP leads to hyperbranched lymphatic vasculatures in pathological conditions without affecting concomitant angiogenesis. In vitro, uPARAP controls LEC migration in response to VEGF-C but not VEGF-A or VEGF-CCys156Ser. uPARAP restricts VEGFR-2/VEGFR-3 heterodimerisation and subsequent VEGFR-2-mediated phosphorylation and inactivation of Crk-II adaptor. uPARAP promotes VEGFR-3 signaling through the Crk-II/JNK/paxillin/Rac1 pathway. Pharmacological Rac1 inhibition in uPARAP knockout mice restores the wild-type phenotype. In summary, our study identifies a molecular regulator of lymphangiogenesis, and uncovers novel molecular features of VEGFR-2/VEGFR-3 crosstalk and downstream signaling during VEGF-C-driven LEC sprouting in pathological conditions. ; info:eu-repo/semantics/published |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| Relation: | uri/info:doi/10.1038/s41467-018-07514-1; uri/info:pii/10.1038/s41467-018-07514-1; uri/info:pmid/30518756; uri/info:pmcid/PMC6281649; https://dipot.ulb.ac.be/dspace/bitstream/2013/286443/4/doi_270070.pdf; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/286443 |
| الاتاحة: | http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/286443 https://dipot.ulb.ac.be/dspace/bitstream/2013/286443/4/doi_270070.pdf |
| رقم الانضمام: | edsbas.3916834E |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |