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Biological activity of substrate-bound basic fibroblast growth factor (FGF2): recruitment of FGF receptor-1 in endothelial cell adhesion contacts

Oncogene volume 21, pages 3889–3897 (2002)Cite this article

Abstract

Substrate-bound FGF2 promotes endothelial cell adhesion by interacting with αvβ3 integrin. Here, endothelial GM7373 cells spread and organize focal adhesion plaques on immobilized FGF2, fibronectin (FN), and vitronectin (VN). αvβ3 integrin, paxillin, focal adhesion kinase, vinculin and pp60src localize in cell-substratum contact sites on FGF2, FN or VN. However, only immobilized FGF2 induces a long-lasting activation of extracellular signal-regulated kinases1/2 (ERK1/2) and cell proliferation that was inhibited by the ERK1/2 inhibitor PD 098059 and the tyrosine kinase (TK) inhibitor tyrphostin 23, pointing to the engagement of FGF receptor (FGFR) at the basal side of the cell. To assess this hypothesis, GM7373 cells were transfected with a dominant negative TK−-ΔFGFR1 mutant (GM7373-ΔFGFR1 cells) or with the full-length receptor (GM7373-FGFR1 cells). Both transfectants adhere and spread on FGF2 but GM7373-ΔFGFR1 cells do not proliferate. Also, parental and GM7373-FGFR1 cells, but not GM7373-ΔFGFR1 cells, undergo morphological changes and increased motility on FGF2-coated plastic. Finally, FGFR1, but not TK−-ΔFGFR1, localizes in cell adhesion contacts on immobilized FGF2. In conclusion, substrate-bound FGF2 induces endothelial cell proliferation, motility, and the recruitment of FGFR1 in cell-substratum contacts. This may contribute to the cross talk among intracellular signaling pathways activated by FGFR1 and αvβ3 integrin in endothelial cells.

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Acknowledgements

This work was supported by MURST (60% and Cofin 2000 to M Rusnati and to M Presta.; Centro di Eccellenza ‘IDET’ to M Presta), CNR (Progetto Finalizzato Biotecnologie), Associazione Italiana per la Ricerca sul Cancro, Istituto Superiore di Sanità (AIDS Project), and Centro per lo Studio del Trattamento dello Scompenso Cardiaco (University of Brescia) to M Presta

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Authors and Affiliations

  1. Department of Biomedical Sciences and Biotechnology, Unit of General Pathology and Immunology, School of Medicine, University of Brescia, Italy

    Elena Tanghetti, Patrizia Dell'Era, Chiara Urbinati, Marco Rusnati & Marco Presta

  2. Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari, Italy

    Roberto Ria

  3. Department of Cytomorphology, University of Cagliari, Italy

    Maria Grazia Ennas

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  1. Elena Tanghetti
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Correspondence to Marco Presta.

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Tanghetti, E., Ria, R., Dell'Era, P. et al. Biological activity of substrate-bound basic fibroblast growth factor (FGF2): recruitment of FGF receptor-1 in endothelial cell adhesion contacts. Oncogene 21, 3889–3897 (2002). https://doi.org/10.1038/sj.onc.1205407

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