Gln-362 of Angiopoietin-2 Mediates Migration of Tumor and Endothelial Cells through Association with alpha 5 beta 1 Integrin
- Gln-362 of Angiopoietin-2 Mediates Migration of Tumor and Endothelial Cells through Association with alpha 5 beta 1 Integrin
- 오승자; 이효선; 이광훈; 이윤숙; 고은; 김경은; 김형찬; Seokkyun Kim; Paul H. Song; Yong-In Kim; Chungho Kim; Sangyeul Han
- Issue Date
- The Journal of biological chemistry
- VOL 289, NO 45-31340
- Angiopoietin-2 (Ang-2) not only regulates angiogenesis by binding to its well known receptor Tie2 on endothelial cells but also controls sprouting of Tie2-negative angiogenic endothelial cells and invasion of Tie2-negative non-endothelial cells by binding to integrins. However, the molecular mechanism of the Ang-2/ integrin association has been unclear. In this study, we found that the Gln-362 residue of Ang-2 was essential for binding to alpha 5 beta 1 integrin. A Q362E Ang-2 mutant, which still bound to Tie2, failed to associate with alpha 5 beta 1 integrin and was unable to activate the integrin downstream signaling of focal adhesion kinase. In addition, unlike wild-type Ang-2, the Q362E Ang-2 mutant was defective in mediating invasion of Tie2-negative glioma or Tie2-positive endothelial cells. Furthermore, the tailpiece domain of the alpha 5 subunit in alpha 5 beta 1 integrin was critical for binding to Ang-2. Taken together, these results provide a novel insight into the mechanism of integrin regulation by Ang-2, which contributes to tumor invasion and endothelial cell migration in a Tie2-independent manner.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.