Recombinant Mouse Integrin alpha V beta 6 Protein, CF

Integrin alpha V beta 6 is one of five alpha V integrins and the sole beta 6 integrin (1, 2). The non-covalent heterodimer of 170 kDa alpha V/CD51 and 95 kDa beta 6 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 alpha V beta 6 is in the N‑terminal head region formed by an interaction of the beta 6 vWFA domain with the alpha V beta‑propeller structure (2). The alpha V 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  alpha V ECD (4), which is cleaved at aa 886 but remains associated, shares 92‑95% aa sequence identity with human and bovine alpha V, while the 687 aa mouse beta 6 ECD (5) shares 90‑96% aa sequence identity with human, rat, bovine, ovine, and porcine  beta 6. Each subunit has a transmembrane sequence and a short cytoplasmic tail connected to the cytoskeleton. The beta 6 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 alpha V beta 6 binds matrix proteins fibronectin and tenascin C (2). It also binds the TGF‑ beta latency‑associated peptide (LAP) and activates TGF‑ beta 1 or TGF‑ beta 3 from large latent complexes (7). This activation requires interaction with LTBP‑1 and fibronectin, and is enhanced by PAR-1 (8, 9). Deletion of beta 6 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 alpha V beta 6 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 alpha V beta 6 as a receptor, and soluble alpha V beta 6 may block virus infectivity in vitro (13, 14).