Recombinant Mouse Integrin alpha 4 beta 1 Protein, CF

Integrin alpha 4 beta 1, also called VLA4, is an integrin family adhesion receptor that shares the beta 1 subunit with eleven other family members and the alpha 4 subunit with Integrin  alpha 4 beta 7 (1-4). The non-covalent heterodimer of 150 kDa alpha 4/CD49d and 130 kDa beta 1/CD29 type I transmembrane glycoprotein subunits mediates cell adhesion to VCAM‑1/CD106 on other cells and the CS-1 fragment of fibronectin in the extracellular matrix (2-4). The alpha 4 extracellular domain (ECD) contains an N-terminal beta ‑propeller structure, followed by domains termed thigh, calf-1 and calf-2 (1). The beta 1 ECD contains a vWFA domain, which interacts with the alpha 4 beta -propeller to form a binding domain when the dimer is in active, extended and open conformation. Each subunit has a transmembrane sequence and a short cytoplasmic tail. The 944 aa mouse alpha 4 ECD shares 85% and 94% aa identity with human and rat alpha 4, respectively, while the 708 aa mouse beta 1 ECD shares 98% aa identity with rat and 93-94% aa identity with human, bovine, porcine, ovine, canine and feline beta 1. Leukocytes (except for neutrophils), erythroid precursors and some non-hematopoietic cells such as epicardial, endothelial and smooth muscle precursors, Schwann cells, and chorionic cells express alpha 4 beta 1 (5-9). Deletion is lethal in the mouse embryo due to faulty placentation and development of the epicardium and coronary vessels (6, 9). In the adult, alpha 4 beta 1 primarily regulates immune cell migration (10-12). Circulating leukocyte alpha 4 beta 1 is rapidly activated by inflamed endothelial cells that present VCAM-1 and chemokines such as SDF-1 (10). This activation facilitates rolling, firm adhesion, and extravasation. In humans, interfering with leukocyte migration via the therapeutic alpha 4 beta 1antibody Natalizumab can reduce the severity of autoimmune disorders such as multiple sclerosis (11). Natalizumab can also mobilize hematopoietic precursors from the bone marrow by impeding their interaction with stromal cell VCAM-1 (7, 11).  During immune cell activation, alpha 4 beta 1 can function as a costimulatory molecule (12, 13).