GENOMIC ORGANIZATION OF THE MOUSE AND HUMAN GENES FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR-B (VEGF-B) AND CHARACTERIZATION OF A 2ND SPLICE ISOFORM

A second isoform and the genomic structures of mouse and human vascula r endothelial growth factor B are described. Both genes consist of sev en coding exons and span about 4 kilobases of DNA. The two identified isoforms of vascular endothelial growth factor B are generated by alte rnative splicing where different, splice acceptor sites in exon 6 intr oduce a frameshift and a partial use of different but overlapping read ing frames, Consequently, the COOK-terminal domains in the two isoform s show no resemblance, Mouse and human cDNA clones for the novel isofo rm 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 glyc osylation and displayed a molecular mass of 32 kDa under reducing cond itions. The protein was expressed as a disulfide-linked homodimer, and heterodimers were generated when coexpressed with vascular endothelia l growth factor. The entirely different COOH-terminal domains in the t wo isoforms of vascular endothelial growth factor B imply that some fu nctional properties of the two proteins are distinct.