Recombinant Mouse Integrin alpha V beta 6 Protein, CF

Integrin alphaV beta6 is one of five alphaV integrins and the sole beta6 integrin (1, 2). The non-covalent heterodimer of 170 kDa alphaV/CD51 and 95 kDa beta6 integrin subunits is expressed exclusively on subsets of epithelial cells, especially during development, after injury or inflammation, or on many carcinomas (2‑5). The ligand interaction site of alphaV beta6 is in the N‑terminal head region formed by an interaction of the beta6 vWFA domain with the alphaV beta‑propeller structure (2). The alphaV subunit contains domains termed thigh, calf, and calf‑2 with a divalent cation‑binding site found at a position equivalent to the “knee”. The 958 aa mouse  alphaV ECD (4), which is cleaved at aa 886 but remains associated, shares 92‑95% aa sequence identity with human and bovine alphaV, while the 687 aa mouse beta6 ECD (5) shares 90‑96% aa sequence identity with human, rat, bovine, ovine, and porcine  beta6. Each subunit has a transmembrane sequence and a short cytoplasmic tail connected to the cytoskeleton. The beta6 C‑terminal 11 amino acid (aa) cytoplasmic sequence transduces a signal, enhancing proliferation and inducing MMP‑9 expression (6). Either “inside‑out” signaling or Mg²⁺ or Mn²⁺ binding unfolds and activates the integrin (1). Active alphaV beta6 binds matrix proteins fibronectin and tenascin C (2). It also binds the TGF‑ beta latency‑associated peptide (LAP) and activates TGF‑ beta1 or TGF‑ beta3 from large latent complexes (7). This activation requires interaction with LTBP‑1 and fibronectin, and is enhanced by PAR-1 (8, 9). Deletion of beta6 ablates tonic inhibition of alveolar macrophages by TGF‑ beta, inhibits intestinal regulatory T cell production, and predisposes mice to inflammatory reactions in the skin, lungs, and intestines where irritations and microbial challenges are frequent (10‑12). High alphaV beta6 expression in carcinomas may contribute to progression through its effects on TGF‑ beta and MMP activity (3). The foot-and-mouth disease virus and several other viruses can use alphaV beta6 as a receptor, and soluble alphaV beta6 may block virus infectivity in vitro (13, 14).