CLONING AND CHARACTERIZATION OF A NOVEL HUMAN GENE-RELATED TO VASCULAR ENDOTHELIAL GROWTH-FACTOR

This paper describes the cloning and characterization of a new member of the vascular endothelial growth Factor (VEGF) gene family, which we have designated VRF for VEGF-related-factor. Sequencing of cDNAs from a human fetal brain library and RT-PCR products from normal and tumor tissue cDNA pools indicate two alternatively spliced messages with op en reading frames of 621 and 564 bp, respectively. The predicted prote ins differ at their carboxyl ends resulting from a shift in the open r eading frame. Both isoforms show strong homology to VEGF at their amin o termini, but only the shorter isoform maintains homology to VEGF at its carboxyl terminus and conserves all 16 cysteine residues of VEGF(1 65). Similarity comparisons of this isoform revealed overall protein i dentity of 48% and conservative substitution of 69% with VEGF(189). VR F is predicted to contain a signal peptide, suggesting that it may be a secreted factor. The VRF gene maps to the D11S750 locus at chromosom e band 11q13, and the protein coding region, spanning similar to 5 kb, is comprised of 8 exons that range in size From 36 to 431 bp. Exons 6 and 7 are contiguous and the two isoforms of VRF arise through altern ate splicing of exon 6. VRF appears to be ubiquitously expressed as tw o transcripts of 2.0 and 5.5 kb; the level of expression is similar am ong normal and malignant tissues.