Recombinant Human Integrin alpha V beta 8 Protein, CF

Integrin alpha V beta 8 is one of five alpha V integrins and the only known beta 8 integrin (1-3). The non-covalent heterodimer of 170 kDa alpha V and ~90 kDa beta 8 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 alpha V integrins, alpha V beta 8 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 alpha V beta 8 to LAP allows proteolytic cleavage by MT1-MMP, which releases active TGF-beta. This mechanism differs from that of alpha V beta 6, the other alpha V 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 alpha V or  beta 8 reveals that alpha V beta 8 is required for vascular morphogenesis in the embryonic brain and yolk sac (4, 14, 15). The 962 aa human alpha V extracellular domain (ECD) shares 92-95% aa sequence identity with mouse, rat and cow alpha V, while the 642 aa human beta 8 ECD shares 92%, 92%, 89%, 87% and 87% aa identity with cow, dog, rabbit, mouse and rat beta 8, respectively. The beta 8 ECD of beta 8 shows low (~35%) aa identity with other integrin beta subunits, and the cytoplasmic tail is unlike any other integrin. The alpha V ECD contains an N-terminal beta - propeller structure, followed by domains termed thigh, calf-1 and calf-2 (1). The beta 8 ECD contains a vWFA domain, which interacts with the alpha V beta -propeller to form a binding domain. Each subunit has a transmembrane sequence and a short cytoplasmic tail.