Recombinant Mouse Integrin alpha 4 beta 1 Protein, CF

Integrin alpha4 beta1, also called VLA4, is an integrin family adhesion receptor that shares the beta1 subunit with eleven other family members and the alpha4 subunit with Integrin  alpha4 beta7 (1-4). The non-covalent heterodimer of 150 kDa alpha4/CD49d and 130 kDa beta1/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 alpha4 extracellular domain (ECD) contains an N-terminal beta‑propeller structure, followed by domains termed thigh, calf-1 and calf-2 (1). The beta1 ECD contains a vWFA domain, which interacts with the alpha4 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 alpha4 ECD shares 85% and 94% aa identity with human and rat alpha4, respectively, while the 708 aa mouse beta1 ECD shares 98% aa identity with rat and 93-94% aa identity with human, bovine, porcine, ovine, canine and feline beta1. 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 alpha4 beta1 (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, alpha4 beta1 primarily regulates immune cell migration (10-12). Circulating leukocyte alpha4 beta1 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 alpha4 beta1antibody 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, alpha4 beta1 can function as a costimulatory molecule (12, 13).