Recombinant Mouse Semaphorin 4D/CD100 Fc Chimera Protein, CF

Semaphorin 4D (Sema4D/CD100, previously sem J, G or C-like 2) is a 150 kDa type I transmembrane glycoprotein of the Class 4 family of transmembrane immune and nervous system semaphorins (1-3). The mouse Sema4D cDNA encodes 861 amino acids (aa) including a 23 aa signal sequence, a 710 aa extracellular domain (ECD) with sema, PSI and immunoglobulin-like domains, a 21 aa transmembrane domain and a 107 aa cytoplasmic domain. Within the ECD portion expressed (aa 24-711), mouse Sema4D shares 93%, 87%, 82% and 78% aa identity with rat, human, porcine and canine Sema4D, respectively. Sema4D is active as a homodimer that occurs via a membrane-proximal intermolecular disulfide (C707) and hydrophobic interactions involving F244 and F246 (4, 5). Proteolysis by metalloproteinases such as TACE/ADAM17 and MMP-14 (MT1-MMP) produces a soluble, active 120 kDa form that is also active as a dimer (5-7). Sema4D, produced by T cells and activated B and dendritic cells, acts through its low affinity receptor CD72 in the immune system (1, 2). CD72 inhibits the antigen presenting cells that express it; this inhibition is relieved by Sema4D binding (8). Sema4D thus causes enhanced B cell survival, differentiation of macrophages and DC, and enhanced T cell antigen priming (2, 8, 9). Sema4D and its high affinity receptor, Plexin B1, are expressed in complimentary patterns in several regions of the brain, and assist in guidance of developing neurons (10). Lower-affinity Sema4D/Plexin B2 binding also enhances neuronal radial and tangential migration (11). Sema4D produced by tumor-associated macrophages binds endothelial cell Plexin B1 to promote tumor angiogenesis, while Sema4D-induced neovascularization and platelet activation is involved in atherosclerosis (3, 6, 7, 12-14). Receptors associated in cis with plexins, such as Met and ErbB2, can alter Sema4D-mediated activities (3).