She, short for Src homology 2 domain containing E protein, was identified in a screen for proteins interacting with Abelson (Abl)-kinase. It is involved in regulating vascular lumen size, with its biological role being related to the Abl signaling pathway [1].

Zebrafish she mutants showed increased endothelial cell number, enlarged dorsal aorta (DA) lumen size and blood flow defects. Overexpression of she in vascular endothelial cells led to a reduced DA lumen diameter, fewer arterial cells and lower endothelial cell proliferation. Chemical inhibition of Abl signaling in zebrafish embryos mimicked the effect of she overexpression and alleviated the she mutant phenotype. In human endothelial umbilical vein cells, SHE knockdown increased vascular tube diameter and phosphorylation of ABL downstream effector CRKL. These suggest that She acts as a negative regulator of Abl signaling, and regulates DA lumen size in part by promoting cldn5a expression [1].

In summary, She is an evolutionarily conserved inhibitor of ABL signaling, playing a crucial role in regulating lumen size during vascular tubulogenesis. The zebrafish she mutant model has been instrumental in revealing these functions of She in vascular development [1].