Systemic Analysis of Tyrosine Phosphorylated Proteins in Angiopoietin-1 Induced Signaling Pathway of Endothelial Cells

详细信息    查看全文

• 作者：Young Mee Kim ; Jawon Seo ; Yung Hee Kim ; Jaeho Jeong ; Hye Joon Joo ; Dong-Hee Lee ; Gou Young Koh ; Kong-Joo Lee
• 刊名：Journal of Proteome Research
• 出版年：2007
• 出版时间：August 2007
• 年：2007
• 卷：6
• 期：8
• 页码：3278 - 3290
• 全文大小：879K
• 年卷期：v.6,no.8(August 2007)
• ISSN：1535-3907

文摘

Angiogenesis is an essential process in physiological and pathological processes and is well-regulatedto maintain the cellular homeostasis by balancing the endothelial cells in proliferation and apoptosis.Angiopoietin-1 (Ang1) regulates angiogenesis as a ligand of Tie 2 receptor tyrosine kinase. However,the regulation pathways are not well-understood. To date, only a few of the signaling molecules involvedin the Tie 2 receptor tyrosine kinase-mediated angiogenesis have been identified. In this study, wesystematically identified tyrosine-phosphorylated proteins in Ang1-induced signaling cascade in humanumbilical vein endothelial cells (HUVECs), employing proteomic analyses combining two-dimensionalgel electrophoresis, Western analysis using phosphotyrosine antibody and mass spectrometry (MALDI-TOF MS and nanoLC-ESI-q-TOF tandem MS). We report here the identification, semiquantitativeanalysis, and kinetic changes of tyrosine-phosphorylated proteins in response to Ang1 in HUVECs andidentified 66 proteins among 69 protein spots showing significant changes. Of these, p54nrb wasvalidated as a molecule involved in cell migration. These results suggest that Ang1 induces stabilizationof neo-vessel network by regulating the phosphorylations of metabolic and structural proteins.