The novel ?4B murine ?4 integrin protein splicing variant inhibits ?4 protein-dependent cell adhesion.

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

SUBMITTER: Kouro H 

PROVIDER: S-EPMC4047406 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature