Fig. 7.

Role of p66Shc in capillary-like network formation in ECs and proposed model. A: HUVECs were seeded on Matrigel-coated plates in culture media containing VEGF for 6 h. Eight random fields per well were imaged, and representative pictures are shown (top). Averaged numbers of capillary tube branches, branching points, and tube length per field are shown (bottom; n = 3). P < 0.05. B: proposed model for novel role of p66Shc in ROS-dependent VEGFR2 signaling and angiogenesis in ECs. VEGF stimulation promotes pS36-pp66Shc formation through ERK/JNK/PKC as well as association of nonphosphorylated form of p66Shc with Rac1, a component of Nox2 NADPH oxidase in ECs. p66Shc is involved in VEGF-induced Rac1 activation and ROS production, thereby promoting VEGFR2 activation in caveolae/lipid rafts, which in turn stimulates angiogenic responses in ECs.