• Hyo Seon Lee, Seung Ja Oh, Kwang-Hoon Lee, Yoon-Sook Lee, Eun Ko, Kyung Eun Kim, Hyung-chan Kim, Seokkyun Kim, Paul H Song, Yong-In Kim, Chungho Kim, and Sangyeul Han.
• From the Bio Therapeutics Lab, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
• J. Biol. Chem. 2014 Nov 7; 289 (45): 31330-40.

AbstractAngiopoietin-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 α5β1 integrin. A Q362E Ang-2 mutant, which still bound to Tie2, failed to associate with α5β1 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 α5 subunit in α5β1 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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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