SH2 domain protein E and ABL signaling regulate blood vessel size

by Jennifer A. Schumacher, Zo ë A. Wright, Diandra Rufin Florat, Surendra K. Anand, Manish Dasyani, Surya Prakash Rao Batta, Valentina Laverde, Kaitlin Ferrari, Laurita Klimkaite, Nina O. Bredemeier, Suman Gurung, Gretchen M. Koller, Kalia N. Aguera, Griffin P. Chadwick, Riley D. Johnson, George E. Davis, Saulius Sumanas Blood vessels in different vascular beds vary in size, which is essential for their function and fluid flow along the vascular network. Molecular mechanisms involved in the formation of a vascular lumen of appropriate size, or tubulogenesis, are still only partially understood.Src homology 2 domain containing E (She) protein was previously identified in a screen for proteins that interact with Abelson (Abl)-kinase. However, its biological role has remained unknown. Here we demonstrate that She and Abl signaling regulate vessel size in zebrafish embryos and human endothelial cell culture. Zebrafishshe mutants displayed increased endothelial cell number and enlarged lumen size of the dorsal aorta (DA) and defects in blood flow, eventually leading to the DA collapse. Vascular endothelial specific overexpression ofshe resulted in a reduced diameter of the DA, which correlated with the reduced arterial cell number and lower endothelial cell proliferation. Chemical inhibition of Abl signaling in zebrafish embryos caused a similar reduction in the DA diameter and alleviated theshe mutant phenotype, suggesting that She acts as a negative regulator of Abl signaling....
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research