Integrin subunit alpha 2 (ITGA2) (ITGA2)

Integrin subunit alpha 2 (ITGA2), also known as CD49b or Glycoprotein Ia, is a transmembrane glycoprotein that forms a non-covalent heterodimer with the beta-1 subunit to create the alpha2beta1 (VLA-2) complex. This heterodimer serves as a primary receptor for extracellular matrix components, specifically collagen and laminin, and is expressed on platelets, epithelial cells, and fibroblasts [NIH, UniProt]. In physiological conditions, it mediates platelet adhesion to injured vessel walls and regulates cell migration and wound healing [PubMed, PNAS]. However, ITGA2 is frequently upregulated in various cancers, including pancreatic, gastric, and breast cancer, where it promotes tumor invasion, metastasis, and resistance to chemotherapy by activating intracellular signaling cascades like the PI3K/AKT and STAT3 pathways [MDPI, Frontiers]. It also plays a role in inflammatory diseases such as rheumatoid arthritis and acts as a receptor for certain viruses like rotavirus [NIH]. Therapeutic targeting of ITGA2, primarily through small molecule inhibitors like E7820 or monoclonal antibodies, aims to disrupt these pathological interactions to treat thrombosis and malignancy [PubMed]. While targeting ITGA2 offers a potentially safer antithrombotic profile compared to other integrin inhibitors, concerns regarding bleeding risks and impaired tissue repair remain important considerations in drug development [PNAS].

Other names

CD49bVLA-2Glycoprotein IaGP IaPlatelet membrane glycoprotein IaCollagen receptor

Allosteric inhibition of the integrin alpha-2 beta-1 heterodimer, blocking the interaction between the alpha-2 I-domain and extracellular matrix ligands such as collagen and laminin, thereby suppressing downstream signaling pathways including PI3K/AKT and STAT3 [PubMed, PNAS].