Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation
Fibroblast growth factors (FGFs) play a critical role in diverse physiological processes and the pathogenesis of diseases. Integrins are involved in FGF signaling, since integrin antagonists suppress FGF signaling. This is called integrin-FGF crosstalk, while the specifics of the crosstalk are uncle...
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-08-01
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| Series: | Medical Sciences |
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| Online Access: | http://www.mdpi.com/2076-3271/1/1/20 |
| _version_ | 1819123865346899968 |
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| author | Seiji Mori Yoshikazu Takada |
| author_facet | Seiji Mori Yoshikazu Takada |
| author_sort | Seiji Mori |
| collection | DOAJ |
| description | Fibroblast growth factors (FGFs) play a critical role in diverse physiological processes and the pathogenesis of diseases. Integrins are involved in FGF signaling, since integrin antagonists suppress FGF signaling. This is called integrin-FGF crosstalk, while the specifics of the crosstalk are unclear. This review highlights recent findings that FGF1 directly interacts with integrin αvβ3, and the resulting integrin-FGF-fibroblast growth factor receptor (FGFR) ternary complex formation is essential for FGF1-induced cell proliferation, migration and angiogenesis. An integrin-binding defective FGF1 mutant (Arg-50 to Glu, R50E) is defective in ternary complex formation and in inducing cell proliferation, migration and angiogenesis, while R50E still binds to the FGF receptor and heparin. In addition, R50E suppressed tumorigenesis in vivo, while wild-type (WT) FGF1 enhanced it. Thus, the direct interaction between FGF1 and integrin αvβ3 is a potential therapeutic target, and R50E is a potential therapeutic agent. |
| first_indexed | 2024-12-22T07:15:08Z |
| format | Article |
| id | doaj.art-47ee77d08abd4839b1815ed62e17d58f |
| institution | Directory Open Access Journal |
| issn | 2076-3271 |
| language | English |
| last_indexed | 2024-12-22T07:15:08Z |
| publishDate | 2013-08-01 |
| publisher | MDPI AG |
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| series | Medical Sciences |
| spelling | doaj.art-47ee77d08abd4839b1815ed62e17d58f2022-12-21T18:34:24ZengMDPI AGMedical Sciences2076-32712013-08-0111203610.3390/medsci1010020medsci1010020Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex FormationSeiji Mori0Yoshikazu Takada1Department of Molecular Pathology, Osaka University Graduate School of Medicine, Division of Health Sciences, 1-7 Yamada-oka, Suita-shi, Osaka 565-0871, JapanDepartments of Dermatology and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USAFibroblast growth factors (FGFs) play a critical role in diverse physiological processes and the pathogenesis of diseases. Integrins are involved in FGF signaling, since integrin antagonists suppress FGF signaling. This is called integrin-FGF crosstalk, while the specifics of the crosstalk are unclear. This review highlights recent findings that FGF1 directly interacts with integrin αvβ3, and the resulting integrin-FGF-fibroblast growth factor receptor (FGFR) ternary complex formation is essential for FGF1-induced cell proliferation, migration and angiogenesis. An integrin-binding defective FGF1 mutant (Arg-50 to Glu, R50E) is defective in ternary complex formation and in inducing cell proliferation, migration and angiogenesis, while R50E still binds to the FGF receptor and heparin. In addition, R50E suppressed tumorigenesis in vivo, while wild-type (WT) FGF1 enhanced it. Thus, the direct interaction between FGF1 and integrin αvβ3 is a potential therapeutic target, and R50E is a potential therapeutic agent.http://www.mdpi.com/2076-3271/1/1/20FGF1integrincrosstalkdominant-negative mutant |
| spellingShingle | Seiji Mori Yoshikazu Takada Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation Medical Sciences FGF1 integrin crosstalk dominant-negative mutant |
| title | Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation |
| title_full | Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation |
| title_fullStr | Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation |
| title_full_unstemmed | Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation |
| title_short | Crosstalk between Fibroblast Growth Factor (FGF) Receptor and Integrin through Direct Integrin Binding to FGF and Resulting Integrin-FGF-FGFR Ternary Complex Formation |
| title_sort | crosstalk between fibroblast growth factor fgf receptor and integrin through direct integrin binding to fgf and resulting integrin fgf fgfr ternary complex formation |
| topic | FGF1 integrin crosstalk dominant-negative mutant |
| url | http://www.mdpi.com/2076-3271/1/1/20 |
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