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The Novel α4B Murine α4 Integrin Protein Splicing Variant Inhibits α4 Protein-dependent Cell Adhesion

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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
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)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正

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