Purification and characterization of a naturally occurring vascular endothelial growth factor.placenta growth factor heterodimer.
Vascular endothelial growth factor (VEGF) is a potent and selective mitogen for endothelial cells that is angiogenic in vivo and induced by hypoxia. A homologous protein, placenta growth factor (PlGF), is also reported to be mitogenic for endothelial cells in culture. The rat GS-9L glioma cell line produces not only VEGF homodimers but also PlGF homodimers and a novel heterodimer composed of VEGF and PlGF subunits. All three dimeric forms were purified to apparent homogeneity, and their structures and mitogenic activities were compared. VEGF.PlGF heterodimers are vascular endothelial cell mitogens nearly as potent as VEGF homodimers. Therefore, some of the biological activities attributed to VEGF homodimers might be mediated by VEGF.PlGF heterodimers. In contrast, pure PlGF homodimers are mitogenic for endothelial cells only at high, possibly non-physiologic concentrations; thus the biological relevance of their mitogenic activity for these cells is not obvious. However, the existence of not only homodimers but also heterodimers clearly extends the similarity between the VEGF/PlGF and the homologous platelet-derived growth factor systems.
DiSalvo
J
J
Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Bayne
M L
ML
Conn
G
G
Kwok
P W
PW
Trivedi
P G
PG
Soderman
D D
DD
Palisi
T M
TM
Sullivan
K A
KA
Thomas
K A
KA
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D003001:Cloning, Molecular; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000302:isolation & purification* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D005910:Glioma; D006133:Growth Substances / Q000096:biosynthesis / Q000302:isolation & purification; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis* / Q000302:isolation & purification* / Q000494:pharmacology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010920:Placenta; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000302:isolation & purification* / Q000494:pharmacology; D055503:Protein Multimerization; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D046911:Macromolecular Substances; C000608036:PGF protein, human; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor