Recombinant Human VEGF 162 Protein

The human VEGF-A gene contains eight exons plus a nontraditional ninth exon in the 3’ UTR (1). The A gene gives rise to multiple splice variants of VEGF-A, ranging from 121 amino acids (aa) to 206 aa in length. All human splice variants contain exons 1-5 and some part of exon 8. Exons 6 and 7 are split into at least two parts, some of which may be included in any one molecule (1-5). The nontraditional 9^th exon is a substitute for exon 8. Incorporation of the 9^th exon results in a non-signaling form of VEGF (5). VEGF₁₆₂ is a VEGF isoform that induces endothelial cell proliferation in vitro and angiogenesis in vivo (5). It is synthesized as a 40-45 kDa disulfide-linked homodimer whose subunits are a product of exons 1-5, 6a, 6b and 8 (5). The three aa difference between VEGF₁₆₅ and VEGF₁₆₂ is attributable to the fact that the 165 form only utilizes exon 7 while the 162 form only utilizes exon 6. Within exon 6, exon 6a contributes 24 aa while exon 6b contributes 17 aa (aa 116‑156 in the mature segment) (2). Exon 6a is not commonly found with exon 6b. In VEGF₁₆₂, exon 6b appears to act as a counterpart to the activity of exon 6a. That is, the product of exon 6a normally promotes VEGF binding to basement membrane while the product of exon 6b promotes VEGF dissociation and solubilization. In this case, VEGF₁₆₂ is notably soluble.