Plcg1 integration of Vegf receptor signaling

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

DESCRIPTION (provided by applicant): Understanding the function and regulation of molecules involved in Vascular endothelial growth factor (Vegf) signaling and it's role in blood vessel development have become of increasing significance since the mechanisms that drive this process are the same as those used by vascular pathologies. A better understanding of this developmental process will be key in the development of therapies and diagnoses of many vascular disorders such as heart disease, cancer, and diabetes. The use of a pliable vertebrate genetic system such as the Zebrafish makes the study of blood vessel development both feasible and efficient. In this proposal we single out phospholipase C gamma 1 (plcg1) as the sole integrator of signals derived from Vegf receptors (Vegfr). Through a series of structure function analysis using mutated forms of plcg1 SH2 domains and mutants in plcg1 activation sites, we will determine the necessity of each of these components for blood vessel development, as well as identify key interactions between plcg1 and Vegfrs that are needed to promote this process.