Objective Interendothelial adherents junctions play a crucial role in the development and maintenance of blood vessel integrity. Null mutation of the endothelial specific VE-adhering gene leads to impairment of vascular remodelling and endothelial survival, which is in part due to the loss of VEGF function as a survival factor in these instants. As it was shown that VE-adhering forms complexes with the VEGF receptor 2, in this project we will investigate the significance of VE-adhering in regulating VEGF function and which role beta-catena plays in this process. In adulation, since VE-adhering is an important determinant of contact inhibition of cell growth in the endothelium, the signalling processes at the basis of this activity will be studied. In order to address these questions endothelial cells cultured from VE adhering deficient mice will be used as a model for transfixion of various VE-adhering mutants in an endothelial background. Mutant proteins will be designed to alter either the binding or the detachment of beta-catena from VE-adhering. Furthermore the involvernent of the p120^ctn binding site and the significance of the extra cellular domain of VE-adhering will be investigated. In a second step, the beta-catena gene will be inactivated in endothelial cells specifically a Crew-Lox approach in vivo and the animal phenotype will be studied. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutation Programme(s) FP5-LIFE QUALITY - Specific Programme for research, technological development and demonstration on "Quality of life and management of living resources", 1998-2002 Topic(s) 1.1.1.-6. - Key action The Ageing Population and Disabilities Call for proposal Data not available Funding Scheme RGI - Research grants (individual fellowships) Coordinator MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH EU contribution No data Address Via Eritrea 62 20157 MILANO Italy See on map Links Website Opens in new window Total cost No data
