First Author | Kouro H | Year | 2014 |
Journal | J Biol Chem | Volume | 289 |
Issue | 23 | Pages | 16389-98 |
PubMed ID | 24755217 | Mgi Jnum | J:215942 |
Mgi Id | MGI:5607377 | Doi | 10.1074/jbc.M114.553610 |
Citation | Kouro H, et al. (2014) The novel alpha4B murine alpha4 integrin protein splicing variant inhibits alpha4 protein-dependent cell adhesion. J Biol Chem 289(23):16389-98 |
abstractText | 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 alpha9 integrin splicing variant, SFalpha9, promotes WT alpha9 integrin-dependent adhesion. In this study, we introduced a new murine alpha4 integrin splicing variant, alpha4B, which has a novel short cytoplasmic tail. In inflamed tissues, the expression of alpha4B, as well as WT alpha4 integrin, was up-regulated. Cells expressing alpha4B specifically bound to VCAM-1 but not other alpha4 integrin ligands, such as fibronectin CS1 or osteopontin. The binding of cells expressing WT alpha4 integrin to alpha4 integrin ligands is inhibited by coexpression of alpha4B. Knockdown of alpha4B in metastatic melanoma cell lines results in a significant increase in lung metastasis. Expression levels of WT alpha4 integrin are unaltered by alpha4B, with alpha4B acting as a regulatory subunit for WT alpha4 integrin by a dominant-negative effect or inhibiting alpha4 integrin activation. |