| First Author | Siemeister G | Year | 1998 |
| Journal | J Biol Chem | Volume | 273 |
| Issue | 18 | Pages | 11115-20 |
| PubMed ID | 9556597 | Mgi Jnum | J:47411 |
| Mgi Id | MGI:1203414 | Doi | 10.1074/jbc.273.18.11115 |
| Citation | Siemeister G, et al. (1998) The alpha-helical domain near the amino terminus is essential for dimerization of vascular endothelial growth factor. J Biol Chem 273(18):11115-20 |
| abstractText | Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and a key mediator of aberrant endothelial cell proliferation and vascular permeability in a variety of human pathological situations such as tumor angiogenesis, diabetic retinopathy, or psoriasis. By amino-terminal deletion analysis and by site-directed mutagenesis we have identified a new domain within the amino-terminal alpha-helix that is essential for dimerization of VEGF. VEGF121 variants containing amino acids 8 to 121 or 14 to 121, respectively, either expressed in Escherichia coli and refolded in vitro, or expressed in Chinese hamster ovary cells, were in a dimeric conformation and showed full binding activity to VEGF receptors and stimulation of endothelial cell proliferation as compared with wild-type VEGF. In contrast, a VEGF121 variant covering amino acids 18 to 121, as well as a variant in which the hydrophobic amino acids Val14, Val15, Phe17, and Met18 within the amphipathic alpha-helix near the amino terminus were replaced by serine, failed to form biological active VEGF dimers. From these data we conclude that a domain between amino acids His12 and Asp19 within the amino-terminal alpha-helix is essential for formation of VEGF dimers, and we propose hydrophobic interactions between VEGF monomers to stabilize or favor dimerization. |
