A novel regulatory function of proteolytically cleaved VEGF-2 for vascular endothelial and smooth muscle cells.
By high throughput sequencing, we have identified a cDNA encoding a polypeptide related to vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in the VEGF/PDGF gene family. It is designated vascular endothelial growth factor 2 (VEGF-2). Similar to VEGF, expression of VEGF-2 mRNA is abundant in vascular smooth muscle cells and several highly vascularized tissues. VEGF-2 protein is expressed as a secreted 52 kDa precursor as well as the 30 kDa amino-terminal and 27 kDa carboxy-terminal cleavage products. The latter two cleavage products are linked via a disulfide bridge (or bridges) and can be copurified. Using copurified 30 and 27 kDa proteins, the effect of VEGF-2 on growth of several cell types, including vascular endothelial and smooth muscle cells, was determined. Our results demonstrate that VEGF-2 protein stimulates the growth of human vascular endothelial cells but inhibits growth of human aortic smooth muscle cells induced by platelet-derived growth factor. These studies establish VEGF-2 as a novel regulator for growth of vascular endothelial and smooth muscle cells.
Hu
J S
JS
Department of Protein Therapeutics, Human Genome Sciences, Inc., Rockville, Maryland 20850, USA.
Hastings
G A
GA
Cherry
S
S
Gentz
R
R
Ruben
S
S
Coleman
T A
TA
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000302:isolation & purification; D016228:Endothelial Growth Factors / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005312:Fetal Blood; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D014162:Transfection; D014471:Umbilical Veins; D042561:Vascular Endothelial Growth Factor B
D002352:Carrier Proteins; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D006131:Growth Inhibitors; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D042561:Vascular Endothelial Growth Factor B