Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner

• DOI: 10.1038/srep45035
• Publication Date: 2017-03-22T12:10:51Z
• Authors: Dimitris Basagiannis; Sofia Zografou; Katerina Galanopo...; Savvas Christofor...
• Keywords: Signalling; Internalization

Abstract VEGFR2 is a critical angiogenic receptor playing key role in vascular homeostasis. Upon activation by VEGF, becomes endocytosed. Internalisation of facilitated, part, through clathrin mediated endocytosis (CME), the which function debated. Here, we confirm contribution CME uptake. However, curiously, find that different approaches inhibition exert contradictory effects on VEGF signalling; knockdown clathrin, or dynamin, overexpression dynamin K44A, do not affect VEGF-induced phosphorylation ERK1/2, while dynasore causes strong inhibition. We resolve this discrepancy showing although inhibits VEGFR2, its inhibitory action ERK1/2 related to attenuation endocytosis; it rather due an off-target effect drug. Dynasore calcium release, signalling event lies upstream implies could be responsible, at least for drug VEGF-to-ERK1/2 signalling. These results raise caution specific inhibiting clathrin- and dynamin-mediated endocytosis, may also molecules, hence influencing interpretation