Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform

A second isoform and the genomic structures of mouse and human vascular endothelial growth factor B are described. Both genes consist of seven coding exons and span about 4 kilobases of DNA. The two identified isoforms of vascular endothelial growth factor B are generated by alternative splicing where different, splice acceptor sites in exon 6 introduce a frameshift and a partial use of different but overlapping reading frames, Consequently, the COOK-terminal domains in the two isoforms show no resemblance, Mouse and human cDNA clones for the novel isoform of vascular endothelial growth factor B encoded a secreted protein of 186 amino acid residues. Expression in transfected cells generated a protein of 25 kDa which upon secretion was modified by O-linked glycosylation and displayed a molecular mass of 32 kDa under reducing conditions. The protein was expressed as a disulfide-linked homodimer, and heterodimers were generated when coexpressed with vascular endothelial growth factor. The entirely different COOH-terminal domains in the two isoforms of vascular endothelial growth factor B imply that some functional properties of the two proteins are distinct.