Purification and Characterization of a Naturally Occurring Vascular Endothelial Growth Factor Placenta Growth Factor Heterodimer

doi:10.1074/jbc.270.13.7717

Purification and Characterization of a Naturally Occurring Vascular Endothelial Growth Factor Placenta Growth Factor Heterodimer (*)

From the Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065

^¶ To whom correspondence should be addressed:
Merck Research Laboratories, Rm. 80W-243, P.O. Box 2000, Rahway, NJ 07065
. Tel.: 908-594-7567; Fax: 908-594-5067; ken_thomas{at}merck.com

↵^§ Current address: Regeneron Pharmaceuticals, Tarrytown, NY 10591.

Abstract

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.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) L40030[GenBank].
↵¹ The abbreviations used are:

VEGF

vascular endothelial growth factor

PlGF

placenta growth factor

PDGF

platelet-derived growth factor

FLT

fms-like tyrosine kinase receptor

KDR

kinase insert domain-containing receptor

HUVE

human umbilical vein endothelial

PAGE

polyacrylamide gel electrophoresis

HPLC

high pressure liquid chromatography

PCR

polymerase chain reaction.
↵² J. DiSalvo, M. L. Bayne, G. Conn, B. Shelton-Inloes, P. W. Kwok, P. G. Trivedi, D. D. Soderman, T. M. Palisi, K. A. Sullivan, and K. A. Thomas, unpublished observations.
- Received September 12, 1994.
- Revision received January 20, 1995.