The Novel alpha 4B Murine alpha 4 Integrin Protein Splicing Variant Inhibits alpha 4 Protein-dependent Cell Adhesion

作者：Kouro Hitomi; Kon Shigeyuki^*; Matsumoto Naoki; Miyashita Tomoe; Kakuchi Ayaka; Ashitomi Dai; Saitoh Kodai; Nakatsuru Takuya; Togi Sumihito; Muromoto Ryuta; Matsuda Tadashi

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289(23): 16389-16398.

DOI：10.1074/jbc.M114.553610

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 alpha 9 integrin splicing variant, SF alpha 9, promotes WT alpha 9 integrin-dependent adhesion. In this study, we introduced a new murine alpha 4 integrin splicing variant, alpha 4B, which has a novel short cytoplasmic tail. In inflamed tissues, the expression of alpha 4B, as well as WT alpha 4 integrin, was up-regulated. Cells expressing alpha 4B specifically bound to VCAM-1 but not other alpha 4 integrin ligands, such as fibronectin CS1 or osteopontin. The binding of cells expressing WT alpha 4 integrin to alpha 4 integrin ligands is inhibited by coexpression of alpha 4B. Knockdown of alpha 4B in metastatic melanoma cell lines results in a significant increase in lung metastasis. Expression levels of WT alpha 4 integrin are unaltered by alpha 4B, with alpha 4B acting as a regulatory subunit for WT alpha 4 integrin by a dominant-negative effect or inhibiting alpha 4 integrin activation.

• 出版日期2014-6-6