• Purity

  >90%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its binding ability in a functional ELISA. When Mouse Laminin I (Catalog # ) is coated at 10 μg/mL, Recombinant Mouse Integrin alpha 6 beta 4 binds with an apparent K    _D <10 nM.  

• Source

  Chinese Hamster Ovary cell line, CHO-derived

  Mouse Integrin alpha 6 (Phe24-Ser1011) Accession # Q61739	His-Pro	GGGSGGGS	Acidic Tail	6-His tag
  Mouse Integrin beta 4 (Asn29-Ser711) Accession # NP_598424	His-Pro	GGGSGGGS	Basic Tail
  N-terminus				C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Phe24 (Integrin alpha 6) & Asn29 (Integrin beta 4)

• Structure / Form

  Noncovalently-linked heterodimer

• Predicted Molecular Mass

  119 kDa (Integrin alpha 6) & 84.6 kDa (Integrin beta 4)

• SDS-PAGE

  100-115 kDa & 135-145 kDa, reducing conditions

Background: Integrin alpha 6 beta 4

Integrin alpha 6 beta 4 is primarily an epithelial and Schwann cell laminin-binding integrin. While the alpha 6 subunit can also pair with beta 1, beta 4 pairs only with alpha 6 (1, 2). Expression of the non-covalent heterodimer composed of ~150 kDa alpha 6/CD49f and 150-200 kDa beta 4/CD104 type I transmembrane glycoprotein subunits is required for hemidesmosome formation (1, 3). The alpha 6 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 beta 4 subunit cytoplasmic domain is unusually long (~1000 aa) and contains four type III fibronectin repeats that bind intracellular hemidesmosomal components (1-4). beta 4 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 alpha 6 heavy chain shares 98% aa sequence identity with rat and 92-93% with human (X1), bovine, and canine  alpha 6. The 684 aa mouse beta 4 ECD shares 96% aa sequence identity with rat and 87‑92% with human, bovine, and equine  beta 4. Mutation of alpha 6 beta 4 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, alpha 6 beta 4 cooperates with dystroglycan to stabilize the myelin sheath, and mediates attachment to the basal lamina (6, 7). alpha 6 beta 4 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 alpha 6 beta 4 expression correlates with invasiveness of carcinomas (1). In carcinomas, it binds IGF-I and the tetraspanin CD151, which promotes phosphorylation of beta 4 by EGF R, disrupting hemidesmosomes and allowing tumor cell migration (1, 11‑14). alpha 6 beta 4 signaling can also amplify tumor production of VEGF, ErbB and SPARC proteins (1, 15‑17).

• References:

1. Wilhelmsen, K. et al. (2006) Mol. Cell. Biol. 26:2877.

2. Kennel, S.J. et al. (1993) Gene 130:209.

3. Schaapveld, R. Q. J. et al. (1998) J. Cell Biol. 142:271.

4. van Leusden, M. R. et al. (1997) Biochem. Biophys. Res. Commun. 235:826.

5. Pulkkinen, L. et al. (1998) Am. J. Hum. Genet. 63:1376.

6. Nodari, A. et al. (2008) J. Neurosci. 28:6714.

7. Amici, S. A. et al. (2006) J. Neurosci. 26:1179.

8. Liadaki, K. et al. (2012) J. Histochem. Cytochem. 60:31.

9. Zhang, X. and E.F. Reed (2012) Hum. Immunol. 73:1239.

10. Liu, C. et al. (2012) PLoS ONE 7:e32060.

11. Fujita, M. et al. (2012) J. Biol. Chem. 287:12491.

12. Wilhelmsen, K. et al. (2007) Mol. Biol. Cell 18:3512.

13. Yang, X. H. et al. (2008) Cancer Res. 68:3204.

14. Frijns, E. et al. (2010) J. Biol. Chem. 285:37650.

15. Lipscomb, E. A. et al. (2005) Cancer Res. 65:10970.

16. Folgiero, V. et al. (2007) Cancer Res. 67:1645.

17. Gerson, K.D. et al. (2012) J. Biol. Chem. 287:9835.

• Entrez Gene IDs:

  3655 (Human); 16407 (Mouse)

• Alternate Names:

  Integrin alpha 6 beta 4