Recombinant Mouse Semaphorin 3B Fc Chimera Protein

Semaphorin 3B (Sema3B; previously Sem A or Sema V) is one of six Class 3 semaphorins that, in the mouse, share 30% - 55% amino acid (aa) identity (1). Class 3 semaphorins are secreted molecules important for guidance of axons and other cells (2, 3). The 500 aa N-terminal sema domain forms a seven-blade beta-propeller similar to that found in integrin molecules. Fourteen conserved cysteine residues and one or more N-glycosylation sites are thought critical for forming the secondary structure (4). The sema domain is followed by a cysteine-knot plexin/semaphorin/integrin (PSI) domain, an Ig-like domain, and a basic domain (5). Covalent dimerization (aa 709) are required for activity of Sema3B (5, 6). Mature mouse Sema3B shares 93% aa identity with rat Sema3B, and 86% aa identity with human, bovine, porcine and equine Sema3B. A potential isoform with a nine aa substitution for aa 138 - 158 has been sequenced (7). Like other Class 3 semaphorins, Sema3B signaling is transduced by a transmembrane plexin-A dimer, which also has a Sema domain and is coupled to kinase pathways (2, 3). Sema3B binds indirectly to plexins, and requires interaction with neuropilins for activity (2, 3). Repulsive signals through Neuropilin-1 (Npn-1) and attractive signals through Neuropilin-2 (Npn-2) have been identified, affecting adhesion molecule activity in opposite directions (2, 8). In tumors, Sema3B competes with VEGF165 for binding to Npn-1, which in part downregulates tumor angiogenesis, inhibits tumor cell proliferation and promotes apoptosis (9, 12). However, it is also proposed to promote dissemination and metastatic progression by stimulating Npn-1 mediated IL-8 secretion in a subset of tumors that overexpress Sema3B (13). In differentiating osteoblasts, Sema3B expression is induced by vitamin D and promotes osteoclastogenesis (14).