Mouse VEGF‑B 186 Biotinylated Antibody

Vascular endothelial growth factor B (VEGF-B; also known as VFR) is a member of the VEGF-PDGF supergene family of growth factor molecules (1‑4). Five mouse members have been identified, including VEGF-A, -B, -C, -D, and PlGF(-2) (1, 5). VEGF family members are disulfide-linked homo- and heterodimeric proteins that are important regulators of vasculogenesis and lymphangiogenesis. Two isoforms of mouse VEGF-B are produced by alternative splicing (6, 7). The long form (VEGF₁₈₆) is 207 amino acids (aa) in length, with a putative 21 aa signal sequence and a 186 aa (32 kDa) mature region. The short form (VEGF₁₆₇) is 188 aa in length, with a 21 aa signal sequence and a 167 aa (21 kDa) mature segment. The two isoforms share the same N-terminal 94 aa residue containing the cysteine knot VEGF homology domain (6‑8). VEGF₁₈₆ is O-glycosylated; VEGF₁₆₇ is not. VEGF₁₆₇ binds heparin; VEGF₁₈₆ does not. Thus, VEGF₁₈₆ is secreted and freely diffusible in tissues (7). However, the VEGF-B₁₆₇ isoform is the predominant form in tissue (9). Mouse VEGF-B₁₈₆ shares 93% and 87% aa identity with bovine and human VEGF‑B₁₈₆, respectively. Mouse VEGF-B₁₆₇ also shares 90% and 88% aa identity with bovine and human VEGF-B₁₆₇, respectively. Unlike VEGF₁₆₇, VEGF-B₁₈₆ can undergo proteolytic processing to generate a partially processed 48 kDa heterodimer (16 kDa and 32 kDa) and a fully processed 32 kDa homodimer (two 16 kDa). Processing appears to occur at Arg 127 of the mature protein (10). VEGF-B can heterodimerize with VEGF (7). Both VEGF-B isoforms can bind to VEGF receptor 1 (VEGF R1), but not VEGF R2 or VEGF R3 (11). VEGF-B167 also binds neuropilin-1, but only the 127 aa processed form of VEGF-B₁₈₆ binds neuropilin-1 (10). As a dimer, the full length VEGF-B₁₈₆ does not interact with neuropilin-1, while any dimer that contains the processed VEGF-B₁₂₇ subunit will interact with neuropilin-1 (10). The importance of differential neuropilin binding is unclear. VEGF-B deficient mice display an atrial conduction deficit (12). On endothelial cells, ligation of VEGF R1 by VEGF-B has been shown to regulate the expression and activity of urokinase type plasminogen activator and plasminogen activator inhibitor 1 (11).