The alpha-helical domain near the amino terminus is essential for dimerization of vascular endothelial growth factor.

The Journal of Biological Chemistry
G SiemeisterG Martiny-Baron

Abstract

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 dime...Continue Reading

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Citations

Mar 7, 2014·Applied Microbiology and Biotechnology·Xue Jun WangRong Yue Cao
Aug 23, 2006·The Journal of Cell Biology·Jiahu WangGordon W Laurie
May 19, 2017·Bioengineering & Translational Medicine·Shiven KapurJennifer R Cochran
Mar 10, 2001·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·O ChavandP E Rakoczy
May 18, 2019·ELife·Sawan Kumar JhaMichael Jeltsch
Nov 22, 2001·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·H HuwerH Isringhaus
Aug 2, 2002·The Journal of Biological Chemistry·Thomas P BoesenTorben Halkier
Oct 11, 2020·Medicinal Research Reviews·Claudia RiccardiDaniela Montesarchio

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