Genomic Organization of the Mouse and Human Genes for Vascular Endothelial Growth Factor B (VEGF-B) and Characterization of a Second Splice Isoform

• Published in: The Journal of biological chemistry Vol. 271; no. 32; pp. 19310 - 19317
• Main Authors: Olofsson, B, Pajusola, K, von Euler, G, Chilov, D, Alitalo, K, Eriksson, U
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 09-08-1996
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; Cell Line; Disulfides - metabolism; DNA, Complementary; Endothelial Growth Factors - genetics; Endothelial Growth Factors - metabolism; Exons; Humans; Introns; Medicin och hälsovetenskap; Mice; Molecular Sequence Data; RNA Splicing; RNA, Messenger - genetics; Sequence Homology, Amino Acid; Transfection; Vascular Endothelial Growth Factor B
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.32.19310

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 COOH-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.