Gln-362 of Angiopoietin-2 Mediates Migration of Tumor and Endothelial Cells through Association with α5β1 Integrin
Open accessAbstract
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.
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Gln(P5) (Gln362 in ANGPT2) interacts with the OH-group of Gln766 in α5Calf1.
“Gln(P5), which corresponds to Gln362 in ANGPT2, a residue previously reported to be crucial in mediating binding to α5 integrin (47), interacts with the OH-group of Gln766 in α5Calf1”
From Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling (2026) · cites this paper as [47]
The ANGPT FLD binds the α5Calf1 domain with high affinity.
“Here, we found that the ANGPT FLD binds the α5Calf1 domain with high affinity and report the crystal structure of the α5Calf1-2 domain alone and in complex with the peptide derived from the ANGPT2 FLD (47).”
From Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling (2026) · cites this paper as [47]
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- Authors
- 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.
- Affiliations
- Samsung (South Korea) (KR)
- Korea University (KR)
- Corresponding author
- Kim, Chungho
- Han, Sangyeul
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 289
- Issue
- 45
- Pages
- 31330-31340
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4223333
- OpenAlex
- W2094193755
- Cited by
- 36
- References
- 27
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 2 · 2015: 1 · 2014: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- angiopoietin-2, alpha5beta1 integrin, integrin binding, focal adhesion kinase signaling, endothelial cell migration, tumor invasion, glioma, angiogenesis
- MeSH terms
- Animals, Cell Adhesion, Cell Movement, Cricetulus, Gene Expression Regulation, Glutamine, Cricetinae, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Plasmids, Integrins, CHO Cells, Protein Structure, Tertiary, Integrin alpha5beta1, Angiopoietin-2, Endothelial Cells, Receptor, TIE-2, Cell Line, Tumor
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