Recombinant Mouse Integrin alpha 6 beta 4 Protein, CF

Integrin alpha6 beta4 is primarily an epithelial and Schwann cell laminin-binding integrin. While the alpha6 subunit can also pair with beta1, beta4 pairs only with alpha6 (1, 2). Expression of the non-covalent heterodimer composed of ~150 kDa alpha6/CD49f and 150-200 kDa beta4/CD104 type I transmembrane glycoprotein subunits is required for hemidesmosome formation (1, 3). The alpha6 subunit contains an I (inhibitory) domain and a cleavage site that creates extracellular domain (ECD) heavy and transmembrane light chains. Mouse and human ubiquitously express the X1 isoform, while alternate splicing in the human ECD also creates X2 and X1X2 isoforms. Cytoplasmic splicing creates A and B isoforms in both mouse and human (4, 5). The beta4 subunit cytoplasmic domain is unusually long (~1000 aa) and contains four type III fibronectin repeats that bind intracellular hemidesmosomal components (1-4). beta4 alternative splicing between repeats 2 and 3 creates isoform 2 (deletion of 65 aa) and 3 (deletion plus insertion of 52 aa), which differ in tissue distribution (2, 5). The 876 aa mouse alpha6 heavy chain shares 98% aa sequence identity with rat and 92-93% with human (X1), bovine, and canine  alpha6. The 684 aa mouse beta4 ECD shares 96% aa sequence identity with rat and 87‑92% with human, bovine, and equine  beta4. Mutation of alpha6 beta4 can cause EB-PA, or epidermolysis bullosa (detachment of epidermis from basement membrane) with pyloric atresia, that is neonatally lethal in humans if severe (1, 3, 5). On Schwann cells, alpha6 beta4 cooperates with dystroglycan to stabilize the myelin sheath, and mediates attachment to the basal lamina (6, 7). alpha6 beta4 is also expressed on vessel‑associated muscle progenitors and on lung vascular endothelial cells, where it binds HLA class I molecules and enhances antigen presentation and cell proliferation (8‑10). High alpha6 beta4 expression correlates with invasiveness of carcinomas (1). In carcinomas, it binds IGF-I and the tetraspanin CD151, which promotes phosphorylation of beta4 by EGF R, disrupting hemidesmosomes and allowing tumor cell migration (1, 11‑14). alpha6 beta4 signaling can also amplify tumor production of VEGF, ErbB and SPARC proteins (1, 15‑17).