title: The novel α4B murine α4 integrin protein splicing variant inhibits α4 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 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.
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kouro
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan kon@pharm.hokudai.ac.jp.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Kakuchi
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ashitomi
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Saitoh
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakatsuru
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan tmatsuda@pharm.hokudai.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D005353:Fibronectins / Q000378:metabolism; D039441:Integrin alpha4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D053495:Osteopontin / Q000378:metabolism; D019154:Protein Splicing; D012333:RNA, Messenger / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005353:Fibronectins; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D053495:Osteopontin; D039441:Integrin alpha4
keywords: Alternative Splicing; Cell Adhesion; Extracellular Matrix; Integrins; Tumor Metastases
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