journal article

Journal Article

Text

Journal of Biological Chemistry. 1999, 274(9), p. 5919-5924

Alternatively Spliced EDA Segment Regulates Fibronectin-dependent Cell Cycle Progression and Mitogenic Signal Transduction

American Society for Biochemistry and Molecular Biology

English

Text

1999-02

https://doi.org/10.1074/jbc.274.9.5919

This research was originally published in the Journal of Biological Chemistry. Ri-ichiroh Manabe, Naoko Oh-e and Kiyotoshi Sekiguchi. Alternatively Spliced EDA Segment Regulates Fibronectin-dependent Cell Cycle Progression and Mitogenic Signal Transduction. J. Biol. Chem. 1999; 274: 5919-5924 © the American Society for Biochemistry and Molecular Biology

Fibronectin (FN) is comprised of multiple isoforms arising from alternative splicing of a single gene transcript. One of the alternatively spliced segments, EDA, is expressed prominently in embryonic development, malignant transformation, and wound healing. We showed previously that EDA+ FN was more potent than EDA− FN in promoting cell spreading and cell migration because of its enhanced binding affinity to integrin α5β1 (Manabe, R., Oh-e, N., Maeda, T., Fukuda, T., and Sekiguchi, K. (1997) J. Cell Biol. 139, 295–307). In this study, we compared the cell cycle progression and its associated signal transduction events induced by FN isoforms with or without the EDA segment to examine whether the EDA segment modulates the cell proliferative potential of FN. We found that EDA+ FN was more potent than EDA− FN in inducing G1-S phase transition. Inclusion of the EDA segment potentiated the ability of FN to induce expression of cyclin D1, hyperphosphorylation of pRb, and activation of mitogen-activated protein kinase extracellular signal regulated kinase 2 (ERK2). EDA+ FN was also more potent than EDA− FN in promoting FN-mediated tyrosine phosphorylation of p130Cas, but not focal adhesion kinase, which occurred in parallel with the activation of ERK2, suggesting that p130Cas may be involved in activation of ERK2. These results indicated that alternative splicing at the EDA region is a novel mechanism that promotes FN-induced cell cycle progression through up-regulation of integrin-mediated mitogenic signal transduction.

71438

Alternatively Spliced EDA Segment Regulates Fibronectin-dependent Cell Cycle Progression and Mitogenic Signal Transduction

American Society for Biochemistry and Molecular Biology

English

1999-02

Journal of Biological Chemistry

274

9

5919

5924

https://doi.org/10.1074/jbc.274.9.5919

https://hdl.handle.net/11094/71438