Genomic organization of human and mouse genes for vascular endothelial growth factor C.
We report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) family. Both VEGF-C genes comprise over 40 kilobase pairs of genomic DNA and consist of seven exons, all containing coding sequences. The VEGF homology domain of VEGF-C is encoded by exons 3 and 4. Exons 5 and 7 encode cysteine-rich motifs of the type C6C10CRC, and exon 6 encodes additional C10CXCXC motifs typical of a silk protein. A putative alternatively spliced rare RNA form lacking exon 4 was identified in human fibrosarcoma cells, and a major transcription start site was located in the human VEGF-C gene 523 base pairs upstream of the translation initiation codon. The upstream promoter sequences contain conserved putative binding sites for Sp-1, AP-2, and NF-kappaB transcription factors but no TATA box, and they show promoter activity when transfected into cells. The VEGF-C gene structure is thus assembled from exons encoding propeptides and distinct cysteine-rich domains in addition to the VEGF homology domain, and it shows both similarities and distinct differences in comparison with other members of the VEGF/PDGF gene family.
Chilov
D
D
Molecular/Cancer Biology Laboratory, Haartman Institute, PL21 (Haartmaninkatu 3), University of Helsinki, Helsinki 00014, Finland.
Kukk
E
E
Taira
S
S
Jeltsch
M
M
Kaukonen
J
J
Palotie
A
A
Joukov
V
V
Alitalo
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D003545:Cysteine; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics*; D005091:Exons; D005354:Fibrosarcoma; D014644:Genetic Variation; D015698:Genomic Library; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D015183:Restriction Mapping; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C
D017931:DNA Primers; D016228:Endothelial Growth Factors; D014157:Transcription Factors; D042582:Vascular Endothelial Growth Factor C; D003545:Cysteine