Project description:RNA sequencing of lung tissue from transgenic mice in order to investigate the effect of a single tyrosine to phenylalanine exchange in the endothelial receptor VEGFR2 at position Y949. This exchange creates a mouse with unleaky blood vessels which is an advantage in several diseases such as cancer and cardiovascular disease.
Project description:Transcriptome analysis was used to identify tumor-independent changes after treatment with different tyrosine kinase inhibitors (TKIs).
Project description:The main goal of the project was to identify proteins binding to vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation site Y1173. Synthetic peptides, phosphorylated or not, covering different tyrosine phosphorylation sites in VEGFR2 were immobilized and incubated with cell lysates from human umbilical vein endothelial cells. Retained proteins were analyzed by mass spectrometry. Proteins specifically binding to pY1173 peptide were categorized with regard to the presence of an Src Homology 2 (SH2) domain and the main hits were validated in intact cells treated or not with VEGF, for their ability to bind to the activated wild type VEGFR2 but not to a mutant Y1173F VEGFR2. The role of the pY1173 binding partners in VEGF-regulated endothelial biology was further examined in vitro and in vivo.