|Detection of Integrin alpha V beta 3 in HUVEC Human Cells by Flow Cytometry. HUVEC human umbilical vein endothelial cells were stained with Mouse Anti-Human Integrin alpha V beta 3 Alexa Fluor® 488‑conjugated Monoclonal Antibody (Catalog # FAB3050G, filled histogram) or isotype control antibody (Catalog # IC002G, open histogram). View our protocol for Staining Membrane-associated Proteins.|
Integrin alpha V beta 3 together with alpha IIb beta 3, constitutes the only known beta 3 Integrins (1-3). The non-covalent heterodimer of 170 kDa alpha V/CD51 and 93 kDa beta 3/CD61 subunits shows wide expression, notably by endothelial cells and osteoclasts (2-4). Each subunit has a transmembrane sequence and a short cytoplasmic tail connected to the cytoskeleton. Active cell surface alpha V beta 3 adheres to matrix proteins including vitronectin, fibronectin, fibrinogen and thrombospondin (2, 3). The ligand binding site of alpha V beta 3 is in the N-terminal head region, formed by interaction of the beta 3 vWFA domain with the alpha V beta-propeller structure (4). The alpha V subunit contributes a thigh and a calf region, while the beta 3 subunit contains a PSI domain and four cysteine-rich I-EGF folds. The alpha V subunit domains termed thigh, calf-1 and calf-2 generate a “knee” region that is bent when the alpha V beta 3 is in its constitutively inactive state. Activation, either by “inside out” signaling or by Mg2+ or Mn2+ binding, extends the Integrin to expose its ligand binding site (1, 4). Two splice variants of beta 3 (b and c) diverge over the last 21 amino acids (aa) and lack cytoplasmic phosphorylation sites (5, 6). Another beta 3 splice variant diverges after the vWFA domain, producing a soluble 60 kDa form in platelets and endothelial cells (7). alpha V beta 3 is essential for the maturation of osteoclasts and their binding and resorption of bone; it also, however, promotes their apoptosis (8, 9). M-CSF R and alpha V beta 3 share signaling pathways during osteoclastogenesis, and deletion of either molecule causes osteopetrosis (8, 9). Also cell entry of several viruses is mediated by alpha V beta 3 (4, 10). The 962 aa human alpha V ECD (11) shares 92‑95% aa sequence identity with mouse, rat and cow alpha V while the 685 aa human beta 3 ECD (12) shares 95% aa identity with horse and dog, and 89‑92% aa identity with mouse, rat and pig beta 3.