Raftlin is recruited by neuropilin-1 to the activated VEGFR2 complex to control proangiogenic signaling
| العنوان: | Raftlin is recruited by neuropilin-1 to the activated VEGFR2 complex to control proangiogenic signaling |
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| المؤلفون: | Asha L Bayliss, Harry Mellor, Ananthalakshmy Sundararaman, Camille Granet |
| المصدر: | Angiogenesis Bayliss, A, Sundararaman, A, Granet, C & Mellor, H 2020, ' Raftlin is recruited by neuropilin-1 to the activated VEGFR2 complex to control proangiogenic signaling ', Angiogenesis . https://doi.org/10.1007/s10456-020-09715-zTest |
| بيانات النشر: | Springer Netherlands, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Physiology, Angiogenesis, intracellular trafficking, Clinical Biochemistry, Neovascularization, Physiologic, Receptor tyrosine kinase, Focal adhesion, 03 medical and health sciences, angiogenesis, 0302 clinical medicine, Endothelial cell, Neuropilin 1, Neuropilin, Human Umbilical Vein Endothelial Cells, Humans, Cell Line, Transformed, biology, Chemistry, VEGF receptor, Membrane Proteins, Kinase insert domain receptor, Cell migration, respiratory system, Vascular Endothelial Growth Factor Receptor-2, Neuropilin-1, Cell biology, Endothelial stem cell, 030104 developmental biology, Multiprotein Complexes, biology.protein, endothelial cell, cardiovascular system, neuropilin, Original Article, 030217 neurology & neurosurgery, Intracellular trafficking, circulatory and respiratory physiology, Signal Transduction |
| الوصف: | Background VEGFR2 (vascular endothelial growth factor receptor 2) is the major pro-angiogenic receptor in endothelial cells. Compared to other members of the receptor tyrosine kinase family, we know relatively few VEGFR2 signaling partners. Our objective was to use mass spectrometry-based proteomics to identify novel binding partners of activated VEGFR2. Methods We created an endothelial cell line stably expressing GFP-tagged VEGFR2 and isolated activated receptor complexes. Analysis by mass spectrometry identified raftlin as a novel binding partner of VEGFR2. Results We found that raftlin is recruited to the activated VEGFR2 complex via the co-receptor Nrp1 (neuropilin-1). We show that raftlin regulates the surface levels of Nrp1 in endothelial cells, controlling the availability of Nrp1 for VEGFR2 interaction. Raftlin stabilizes active VEGFR2 at the cell surface by inhibiting endocytosis of the activated receptor. Raftlin also promotes recycling of internalized VEGFR2 to the cell surface. Raftlin alters the signaling outcomes of VEGFR2 activation, inhibiting the activation of p38 and FAK (focal adhesion kinases) specifically. Both pathways are linked to cell migration in endothelial cells, and raftlin inhibits endothelial cell migration in response to VEGF. Conclusion Nrp1 is an important co-receptor for VEGFR2; however, its functions are still only partially understood. We show that raftlin works with Nrp1 in endothelial cells to control intracellular trafficking of the activated VEGFR2. This modulates the response to VEGF and controls endothelial cell migration. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1573-7209 0969-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f63f61eaad5d0ea2fa2f625dbe3d243Test http://europepmc.org/articles/PMC7311514Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5f63f61eaad5d0ea2fa2f625dbe3d243 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15737209 09696970 |
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