VEGF162, a new heparin-binding vascular endothelial growth factor splice form that is expressed in transformed human cells.
The splice forms of vascular endothelial growth factor (VEGF) differ in biological properties such as the receptor types that they recognize and their interaction with heparan sulfate proteoglycans. We have identified a new VEGF mRNA splice form encoding a VEGF species containing 162 amino acids (VEGF(162)) in human A431 ovarian carcinoma cells. This novel mRNA contains the peptides encoded by exons 1-5, 6A, 6B, and 8 of the VEGF gene. Recombinant VEGF(162) is biologically active. It induces proliferation of endothelial cells in vitro and angiogenesis in vivo as determined by the alginate bead assay. VEGF(162) binds less efficiently than VEGF(145) but more efficiently than VEGF(165) to a natural basement membrane produced by corneal endothelial cells. VEGF(138), an artificial VEGF form that contains exon 6B but lacks exons 6A and 7, did not bind to this basement membrane at all, indicating that exon 6B probably interferes with the interaction of exon 6A with heparin and heparan sulfate proteoglycans.
Lange
Tali
T
Department of Cell Biology and Anatomy, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, PO Box 9697, 1 Efron Street, Haifa 31096, Israel.
Guttmann-Raviv
Noga
N
Baruch
Limor
L
Machluf
Marcelle
M
Neufeld
Gera
G
D000818:Animals; D002461:Cell Line, Transformed; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006493:Heparin / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012326:RNA Splicing; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006493:Heparin