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Title: Genetic, biochemical and cellular studies on VEGF receptor protein-protein interactions and intracellular signalling in human endothelial cells
Author: Bao, Leyuan
ISNI:       0000 0004 2718 6888
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2011
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The vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in angiogenesis and vascular physiology in higher eukaryotes such as vertebrates. Although intracellular signalling pathways linked to VEGFR2 activation have been well characterised, there is a lack of knowledge on membrane and cytosolic effectors that interact with VEGFR2. To address this problem, I have used a novel membrane protein yeast 2-hybrid (Y2H) screen to identify novel factors that interact with membrane VEGFR2. By screening a human primary endothelial cDNA library, six potential VEGFR2-binding proteins were isolated. One candidate was the SlOO calcium-binding protein A6 (SlOOA6). SlOOA6 is an abundant protein present in both the nucleus and cytoplasm of endothelial cells. The interaction between VEGFR2 and SlOOA6 was found to be calcium-dependent. Calcium dependent-translocation of S lOOA6 from the nucleus caused eo-distribution with VEGFR2 in punctate vesicles. Depletion of SI OOA6 protein levels using RNA interference perturbed VEGF-A-stimulated VEGFR2 activation and phosphorylation, cell proliferation, cell migration and angiogenesis. Taken together, the work in this thesis suggests that S lOOA6 is a novel binding partner for VEGFR2 and regulates intracellular signalling and angiogenesis. Thus SlOOA6 could be a new target in the treatment of vascular disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available