Human CD42b/GPIb  alpha Antibody

Platelet glycoprotein Ib alpha chain (GPIb  alpha), also known as CD42b alpha, is a 145 kDa type I transmembrane protein that is a member of the leucine-rich repeat (LRR) family of ligand binding proteins (1‑3). It is expressed by platelets as the ligand-binding subunit of the platelet GPIb-IX-V complex (4). Human GPIb  alpha contains a 16 amino acid (aa) signal sequence, a 489 aa extracellular domain (ECD), a 21-aa transmembrane domain, and a 100 aa cytoplasmic region. The ECD contains 8 LRRs, with # 2, 3, and 4 having been demonstrated to regulate shear-dependent adhesion to von Willebrand factor (vWF) (5, 6). The LRRs are followed by a thrombin-binding anionic region that includes three sulfated tyrosines, a sialomucin domain with N- and O-linked carbohydrates, and two cysteines near the membrane that allow dimerization with GP1b  alpha beta (1‑6). Four human isoforms with 1 to 4 repeats of aa 398‑411 within the sialomucin domain of mature GPIb  alpha are known to exist but have unknown significance (7). The ECD of human GPIb  alpha shares 48‑51% aa identity with mouse, rat, bovine, and canine GPIb  alpha. The metalloproteinase TACE/ADAM17 constitutively and inducibly cleaves GPIb  alpha, between Gly480 and Val481. This releases a soluble form called glycocalicin that circulates at ~2 μg/mL (8, 9). GPIb  alpha binding to ligands such as thrombin, kininogen, and coagulation factors XI and XII helps to initiate platelet activation and coordinate the coagulation cascade (1, 10‑12). Binding of GPIb  alpha to vWF or thrombospondin in the plasma or matrix, vWF or P-selectin on endothelial cells, or the integrin  alphaM beta2 (MAC-1) on myeloid cells, controls response to vascular injury (1, 13). Bernard-Soulier syndrome and platelet-type von Willebrand disease are platelet function disorders that can be caused by mutations in GPIb  alpha (1, 14).