Gln-362 of angiopoietin-2 mediates migration of tumor and endothelial cells through association with α5β1 integrin

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, Sangyeul Han

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14 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)31330-31340
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number45
DOIs
Publication statusPublished - 2014 Nov 7

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Lee, H. S., Oh, S. J., Lee, K. H., Lee, Y. S., Ko, E., Kim, K. E., Kim, H. C., Kim, S., Song, P. H., Kim, Y. I., Kim, C., & Han, S. (2014). Gln-362 of angiopoietin-2 mediates migration of tumor and endothelial cells through association with α5β1 integrin. Journal of Biological Chemistry, 289(45), 31330-31340. https://doi.org/10.1074/jbc.M114.572594