Recombinant Human Integrin alpha 4 beta 7/LPAM 1 Protein, CF

Integrin alpha4 beta7 is an integrin family adhesion receptor that shares subunits with alpha4 beta1 (VLA4) and the E-Cadherin receptor, alphaE beta7 (1). It is a non-covalent heterodimer composed of two type I transmembrane glycoprotein subunits, a 150 kDa alpha4 (CD49d) subunit and a 130 kDa beta7 subunit (2, 3). The alpha4 extracellular domain (ECD) contains an N-terminal beta-propeller structure followed by thigh, calf-1, and calf-2 domains (1). The beta7 ECD contains a vWFA domain, which interacts with the
alpha4 beta-propeller to form a binding domain. Metal ion binding sites termed MIDAS and LIMBS promote firm adhesion, and another site termed ADMIDAS is a negative regulatory site that promotes rolling (4-6). The human alpha4 ECD shares 85% amino acid sequence identity with the mouse, rat, and canine alpha4 ECD. The human beta7 ECD shares 88% and 87% amino acid sequence identity with the rat and mouse beta7 ECD, respectively. Integrin alpha4 beta7 binds the mucosal addressin MAdCAM-1, as well as VCAM-1 and Fibronectin (7). Integrin alpha4 beta7, which is critical for homing to intestinal mucosa, is induced during T cell activation in Peyer’s patches or mesenteric lymph nodes (8, 9). Its expression requires signals from local dendritic and stromal cells, including secreted retinoic acid (10, 11). The HIV-1 envelope protein gp120 binds to the active form of Integrin alpha4 beta7, and this may or may not account for the concentration of HIV-1 virus in the gut-associated lymphoid tissue (GALT) (12-14). Integrin  alpha4 beta7 may also be involved in lymphocyte trafficking in acute intestinal graft vs. host disease (GVHD) (15).