Role of Disabled protein 2 (Dab2) in Vascular Endothelial Growth Factor Receptor‐2 signaling, trafficking, and vascular morphogenesis

Abstract

The formation of blood vessels occurs through the process of vasculogenesis or angiogenesis. Angiogenesis plays a crucial role physiological and pathological conditions. Vascular endothelial growth factor receptor 2 (VEGFR2) is one of the key regulators of angiogenesis. Plasma membrane (PM) level of VEGFR2 is regulated by endocytosis and secretory transport processess. VEGF‐binding to VEGFR2 induces phosphorylation of the receptor, endocytosis, and signal transduction process that leads to vascular morphogenesis. Disabled protein 2 (Dab2) is a cytosolic adaptor protein known to function in endocytosis, cell adhesion, and hematopoetic cell differentiation. However, how Dab2 regulates VEGFR2 function at the PM and endosomal level is still not clear. Our results show that depletion of Dab2 decreases VEGFR2 levels and VEGF‐induced phosphorylation of the receptor. Moreover, Dab2 knockdown cells show loss of cell‐cell junction and an inability to form tube structures in response to VEGF stimulation. Thus, our data demonstrate that Dab2 may function in the vascular morphogenesis by regulating VEGFR2 phosphorylation and trafficking.