Direct binding of integrin αvβ3 to FGF1 plays a role in FGF1 signaling

Seiji Mori, Chun Yi Wu, Satoshi Yamaji, Jun Saegusa, Biao Shi, Zi Ma, Yasuko Kuwabara, Kit S. Lam, R. Rivkah Isseroff, Yoko K. Takada, Yoshikazu Takada

研究成果: 雜誌貢獻文章

77 引文 (Scopus)

摘要

Integrins play a role in fibroblast growth factor (FGF) signaling through cross-talk with FGF receptors (FGFRs), but the mechanism underlying the cross-talk is unknown. We discovered that FGF1 directly bound to soluble and cell-surface integrin αvβ3 (KD about 1 μM). Antagonists to αvα3 (monoclonal antibody 7E3 and cyclic RGDfV) blocked this interaction. αvβ3 was the predominant, if not the only, integrin that bound to FGF1, because FGF1 bound only weakly to several β1 integrins tested. We presented evidence that the CYDMKTTC sequence (the specificity loop) within the ligand-binding site of β3 plays a role in FGF1 binding. We found that the integrin-binding site of FGF1 overlaps with the heparin-binding site but is distinct from the FGFR-binding site using docking simulation and mutagenesis. We identified an FGF1 mutant (R50E) that was defective in integrin binding but still bound to heparin and FGFR. R50E was defective in inducing DNA synthesis, cell proliferation, cell migration, and chemotaxis, suggesting that the direct integrin binding to FGF1 is critical for FGF signaling. Nevertheless, R50E induced phosphorylation of FGFR1 and FRS2α and activation of AKT and ERK1/2. These results suggest that the defect in R50E in FGF signaling is not in the initial activation of FGF signaling pathway components, but in the later steps in FGF signaling. We propose that R50E is a useful tool to identify the role of integrins in FGF signaling.

原文英語
頁(從 - 到)18066-18075
頁數10
期刊Journal of Biological Chemistry
283
發行號26
DOIs
出版狀態已發佈 - 六月 27 2008
對外發佈Yes

指紋

Fibroblast Growth Factor 1
Integrins
Fibroblast Growth Factors
Fibroblast Growth Factor Receptors
Binding Sites
Chemical activation
Mutagenesis
Phosphorylation
Cell proliferation
Chemotaxis
Cell Movement
Heparin
Monoclonal Antibodies
Cell Proliferation
Ligands
Defects
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

引用此文

Mori, S., Wu, C. Y., Yamaji, S., Saegusa, J., Shi, B., Ma, Z., ... Takada, Y. (2008). Direct binding of integrin αvβ3 to FGF1 plays a role in FGF1 signaling. Journal of Biological Chemistry, 283(26), 18066-18075. https://doi.org/10.1074/jbc.M801213200

Direct binding of integrin αvβ3 to FGF1 plays a role in FGF1 signaling. / Mori, Seiji; Wu, Chun Yi; Yamaji, Satoshi; Saegusa, Jun; Shi, Biao; Ma, Zi; Kuwabara, Yasuko; Lam, Kit S.; Isseroff, R. Rivkah; Takada, Yoko K.; Takada, Yoshikazu.

於: Journal of Biological Chemistry, 卷 283, 編號 26, 27.06.2008, p. 18066-18075.

研究成果: 雜誌貢獻文章

Mori, S, Wu, CY, Yamaji, S, Saegusa, J, Shi, B, Ma, Z, Kuwabara, Y, Lam, KS, Isseroff, RR, Takada, YK & Takada, Y 2008, 'Direct binding of integrin αvβ3 to FGF1 plays a role in FGF1 signaling', Journal of Biological Chemistry, 卷 283, 編號 26, 頁 18066-18075. https://doi.org/10.1074/jbc.M801213200
Mori, Seiji ; Wu, Chun Yi ; Yamaji, Satoshi ; Saegusa, Jun ; Shi, Biao ; Ma, Zi ; Kuwabara, Yasuko ; Lam, Kit S. ; Isseroff, R. Rivkah ; Takada, Yoko K. ; Takada, Yoshikazu. / Direct binding of integrin αvβ3 to FGF1 plays a role in FGF1 signaling. 於: Journal of Biological Chemistry. 2008 ; 卷 283, 編號 26. 頁 18066-18075.
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AU - Shi, Biao

AU - Ma, Zi

AU - Kuwabara, Yasuko

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