Recombinant Human Integrin alpha V beta 8 Protein, CF

Integrin alphaV beta8 is one of five alphaV integrins and the only known beta8 integrin (1-3). The non-covalent heterodimer of 170 kDa alphaV and ~90 kDa beta8 integrin type I transmembrane glycoprotein subunits is expressed in yolk sac, placenta, brain perivascular astrocytes, Schwann cells, renal glomerular mesangial cells and pulmonary epithelial cells (3-7). Unlike other alphaV integrins, alphaV beta8 does not appear to assume different activation states, and the cytoplasmic tail does not connect to the cytoskeleton (3, 8). It binds ligands containing an RGD motif, including vitronectin, fibrin and the latency associated peptide (LAP) of the latent TGF-beta complex (7-12). High affinity binding of alphaV beta8 to LAP allows proteolytic cleavage by MT1-MMP, which releases active TGF-beta. This mechanism differs from that of alphaV beta6, the other alphaV integrin which can activate TGF-beta from latency through non-proteolytic mechanisms (13). Downstream effects of TGF-beta activation include control of cell growth and associated vascularization (10-13). Deletion of either alphaV or  beta8 reveals that alphaV beta8 is required for vascular morphogenesis in the embryonic brain and yolk sac (4, 14, 15). The 962 aa human alphaV extracellular domain (ECD) shares 92-95% aa sequence identity with mouse, rat and cow alphaV, while the 642 aa human beta8 ECD shares 92%, 92%, 89%, 87% and 87% aa identity with cow, dog, rabbit, mouse and rat beta8, respectively. The beta8 ECD of beta8 shows low (~35%) aa identity with other integrin beta subunits, and the cytoplasmic tail is unlike any other integrin. The alphaV ECD contains an N-terminal beta- propeller structure, followed by domains termed thigh, calf-1 and calf-2 (1). The beta8 ECD contains a vWFA domain, which interacts with the alphaV beta-propeller to form a binding domain. Each subunit has a transmembrane sequence and a short cytoplasmic tail.