Vascular endothelial growth factor receptor 2 (VEGFR2) is a heavily N-glycosylated pro-angiogenic receptor tyrosine kinase. Stimulation of the receptor by vascular endothelial growth factor (VEGF) induces quiescent endothelial cells to proliferate and sprout, and VEGFR2 signaling is also required for tumor growth and metastasis. In a new paper in the Journal of Biological Chemistry by Kevin Brown Chandler and colleagues in the Costello and Rahimi laboratories demonstrated that the glycosylation status of VEGFR2 alters signaling through the receptor. Specifically, sialic acid-capped N-glycans at site N247 oppose ligand-mediated receptor activation, whereas asialo-glycans (lacking sialic acid) favor VEGFR2 activation.