Gln-362 of angiopoietin-2 mediates migration of tumor and endothelial cells through association with α5ß1 integrin.
J Biol Chem
; 289(45): 31330-40, 2014 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-25237190
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 α5ß1 integrin. A Q362E Ang-2 mutant, which still bound to Tie2, failed to associate with α5ß1 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 α5ß1 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.
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Base de dados:
MEDLINE
Assunto principal:
Integrina alfa5beta1
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Células Endoteliais
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Receptor TIE-2
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Angiopoietina-2
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Glutamina
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Neoplasias
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article