Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice

• DOI: 10.1073/pnas.0404984102
• Publication Date: 2005-01-12T03:13:35Z
• Authors: Yoshiko Sakurai; Kaori Ohgimoto; Yuki Kataoka; Nobuaki Yoshida; Masabumi Shibuya
• Keywords: Vasculogenesis

Flk-1 (human counterpart, KDR) tyrosine kinase, which is one of the two VEGF receptors, crucial for vascular development. Recently, we showed that, among residues KDR, 1175 (Y1175, corresponding to Y1173 in murine Flk-1) and Y1214 (Y1212 are autophosphorylated response VEGF, that Y1175 important VEGF-dependent phospholipase Cγ/PKC/mitogen-activated protein kinase activation leading DNA synthesis cultured endothelial cells. However, importance these Flk-1/KDR vivo not yet known. To examine role , generated knock-in mice substituting Y1212 gene with phenylalanine, respectively. As a result, 1173F homozygous died between embryonic days 8.5 9.5 without any organized blood vessels or yolk sac islands, hematopoietic progenitors were severely reduced, similar case null mice. In contrast, 1212F viable fertile. These results suggest signaling via essential development during embryogenesis.