دورية أكاديمية

Chemical Inhibitors of Dynamin Exert Differential Effects in VEGF Signaling

التفاصيل البيبلوغرافية
العنوان: Chemical Inhibitors of Dynamin Exert Differential Effects in VEGF Signaling
المؤلفون: Dimitris Basagiannis, Sofia Zografou, Evangeli Goula, Despoina Gkeka, Evangelos Kolettas, Savvas Christoforidis
المصدر: Cells, Vol 10, Iss 5, p 997 (2021)
بيانات النشر: MDPI AG, 2021.
سنة النشر: 2021
المجموعة: LCC:Cytology
مصطلحات موضوعية: cell signaling, endocytosis, vesicular trafficking, dynamin, inhibitors, endothelial cell biology, Cytology, QH573-671
الوصف: VEGFR2 is the main receptor and mediator of the vasculogenic and angiogenic activity of VEGF. Activated VEGFR2 internalizes through clathrin-mediated endocytosis and macropinocytosis. As dynamin is a key regulator of the clathrin pathway, chemical inhibitors of dynamin are commonly used to assess the role of the clathrin route in receptor signaling. However, drugs may also exert off-target effects. Here, we compare the effects of three dynamin inhibitors, dynasore, dyngo 4a and dynole, on VEGFR2 internalization and signaling. Although these drugs consistently inhibit clathrin-mediated endocytosis of both transferrin (a typical cargo of this route) and VEGFR2, surprisingly, they exert contradictory effects in receptor signaling. Thus, while dynasore has no effect on phosphorylation of VEGFR2, the other two drugs are strong inhibitors. Furthermore, although dyngo does not interfere with phosphorylation of Akt, dynasore and dynole have a strong inhibitory effect. These inconsistent effects suggest that the above dynamin blockers, besides inhibiting dynamin-dependent endocytosis of VEGFR2, exert additional inhibitory effects on signaling that are independent of endocytosis; i.e., they are due to off-target effects. Using a recently developed protocol, we comparatively validate the specificity of two endocytic inhibitors, dynasore and EIPA. Our findings highlight the importance of assessing whether the effect of an endocytic drug on signaling is specifically due to its interference with endocytosis or due to off-targets.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2073-4409
Relation: https://www.mdpi.com/2073-4409/10/5/997; https://doaj.org/toc/2073-4409
DOI: 10.3390/cells10050997
URL الوصول: https://doaj.org/article/93ca219adfce4200bcdfb2ebce8676f2
رقم الأكسشن: edsdoj.93ca219adfce4200bcdfb2ebce8676f2
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20734409
DOI:10.3390/cells10050997