Akt Takes Center Stage in Angiogenesis Signaling

Abstract

The serine/threonine kinase Akt, also named protein kinase B, plays a central role in promoting the survival of a wide range of cell types.1 In this issue of Circulation Research , Kim et al2 report that angiopoietin-1 (Ang1) activates this survival kinase and thereby inhibits endothelial cell apoptosis. Ang1 was recently identified as the specific ligand for the Tie receptor family, which during embryonic blood vessel formation is required for vascular remodeling and vessel integrity.3 Mechanistically, Ang1 acts via stimulation of the Tie2 receptor. Upon activation, tyrosine phosphorylation of the Tie2 receptor (most probably at Tyr 11014 ) induces the association and activation of the phosphatidylinositol 3′kinase with subsequent activation of Akt.2 These findings complement previous studies, which demonstrated that vascular endothelial growth factor (VEGF) via the KDR/Flt-1 receptor also stimulates Akt and thereby promotes endothelial cell survival.5 6 Moreover, potent inhibitors of endothelial cell apoptosis such as shear stress or insulin activate Akt.7 8 Thus, activation of Akt seems to be a general antiapoptotic mechanism induced by proangiogenic stimuli. Because apoptosis of endothelial cells counteracts angiogenesis, one may …