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The Novel α4B Murine α4 Integrin Protein Splicing Variant Inhibits α4 Protein-dependent Cell Adhesion
Title: | The Novel α4B Murine α4 Integrin Protein Splicing Variant Inhibits α4 Protein-dependent Cell Adhesion |
Authors: | Kouro, Hitomi Browse this author | Kon, Shigeyuki Browse this author →KAKEN DB | Matsumoto, Naoki Browse this author | Miyashita, Tomoe Browse this author | Kakuchi, Ayaka Browse this author | Ashitomi, Dai Browse this author | Saitoh, Kodai Browse this author | Nakatsuru, Takuya Browse this author | Togi, Sumihito Browse this author | Muromoto, Ryuta Browse this author →KAKEN DB | Matsuda, Tadashi Browse this author →KAKEN DB |
Keywords: | Alternative Splicing | Cell Adhesion | Extracellular Matrix | Integrins | Tumor Metastases |
Issue Date: | Jun-2014 |
Journal Title: | Journal of Biological Chemistry |
Volume: | 289 |
Issue: | 23 |
Start Page: | 16389 |
End Page: | 16398 |
Publisher DOI: | 10.1074/jbc.M114.553610 |
Abstract: | Integrins affect the motility of multiple cell types to control cell survival, growth, or differentiation, which are mediated by cell-cell and cell-extracellular matrix interactions. We reported previously that the α9 integrin splicing variant, SFα9, promotes WT α9 integrin-dependent adhesion. In this study, we introduced a new murine α4 integrin splicing variant, α4B, which has a novel short cytoplasmic tail. In inflamed tissues, the expression of α4B, as well as WT α4 integrin, was up-regulated. Cells expressing α4B specifically bound to VCAM-1 but not other α4 integrin ligands, such as fibronectin CS1 or osteopontin. The binding of cells expressing WT α4 integrin to α4 integrin ligands is inhibited by coexpression of α4B. Knockdown of α4B in metastatic melanoma cell lines results in a significant increase in lung metastasis. Expression levels of WT α4 integrin are unaltered by α4B, with α4B acting as a regulatory subunit for WT α4 integrin by a dominant-negative effect or inhibiting α4 integrin activation. |
Rights: | This research was originally published in Journal of Biological Chemistry. Kouro, Hitomi; Kon, Shigeyuki; Matsumoto, Naoki; Miyashita, Tomoe; Kakuchi, Ayaka; Ashitomi, Dai; Saitoh, Kodai; Nakatsuru, Takuya; Togi, Sumihito; Muromoto, Ryuta; Matsuda, Tadashi. The novel α4B murine α4 integrin protein splicing variant inhibits α4 protein-dependent cell adhesion. 2014. Vol.289 pp16389-16398. © the American Society for Biochemistry and Molecular Biology. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/59221 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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