PMID: 9539788May 16, 1998Paper

An antagonistic vascular endothelial growth factor (VEGF) variant inhibits VEGF-stimulated receptor autophosphorylation and proliferation of human endothelial cells

Proceedings of the National Academy of Sciences of the United States of America
G SiemeisterG Martiny-Baron

Abstract

Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique specificity for endothelial cells 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, rheumatoid arthritis, or psoriasis. VEGF is a symmetric homodimeric molecule with two receptor binding interfaces lying on each pole of the molecule. Herein we report on the construction and recombinant expression of an asymmetric heterodimeric VEGF variant with an intact receptor binding interface at one pole and a mutant receptor binding interface at the second pole of the dimer. This VEGF variant binds to VEGF receptors but fails to induce receptor activation. In competition experiments, the heterodimeric VEGF variant antagonizes VEGF-stimulated receptor autophosphorylation and proliferation of endothelial cells. A 15-fold excess of the heterodimer was sufficient to inhibit VEGF-stimulated endothelial cell proliferation by 50%, and a 100-fold excess resulted in an almost complete inhibition. By using a rational approach that is based on the structure of VEGF, we have shown the feasibility to construct a VEGF variant that acts as an VEG...Continue Reading

References

Sep 30, 1992·Biochemical and Biophysical Research Communications·B I TermanP Böhlen
Mar 31, 1992·Biochemical and Biophysical Research Communications·K WeindelH A Weich
Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D MaglioneM G Persico
Jan 1, 1990·Methods in Enzymology·F W StudierJ W Dubendorff
Dec 1, 1990·Genes & Development·M MercolaC D Stiles
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·L P AielloL E Smith
Jan 5, 1995·Biochimica Et Biophysica Acta·K P ClaffeyB M Spiegelman
Dec 1, 1995·Current Opinion in Biotechnology·G Martiny-Baron, D Marmé
Jan 12, 1996·The Journal of Biological Chemistry·K A Thomas
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·B OlofssonU Eriksson
May 15, 1996·Biochemical and Biophysical Research Communications·G SiemeisterG Martiny-Baron
Apr 17, 1997·Nature·W Risau
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y A MullerA M de Vos
Dec 1, 1996·Trends in Cell Biology·G Breier, W Risau

❮ Previous
Next ❯

Citations

Aug 8, 2008·Annals of Surgical Oncology·Charlotte F J M PeetersTheo J M Ruers
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Niv PapoJennifer R Cochran
Aug 19, 2007·Bulletin of Mathematical Biology·Harsh V JainTrachette L Jackson
Mar 22, 2005·American Journal of Respiratory and Critical Care Medicine·Rainer KrebsKarl B Lemström
Aug 19, 2006·American Journal of Respiratory and Critical Care Medicine·Jussi M TikkanenKarl B Lemström
Aug 26, 2006·American Journal of Respiratory and Critical Care Medicine·Mark V AvdalovicDallas M Hyde
Jan 20, 2010·Journal of Neuropathology and Experimental Neurology·Heike BeckKarl H Plate
Aug 5, 2008·Trends in Biotechnology·Douglas S JonesJennifer R Cochran
Apr 20, 2007·Biophysical Chemistry·Feilim Mac Gabhann, Aleksander S Popel
Sep 24, 2013·Scientific Reports·Maria KarlssonWilfried Weber
Aug 6, 2013·Journal of Cellular Biochemistry·Richard J Galas, Julie C Liu
Nov 11, 2015·Cellular and Molecular Life Sciences : CMLS·Filippa FleetwoodJohn Löfblom
Mar 24, 2007·The Journal of Medical Investigation : JMI·Hideki TomimotoSaburo Sone
Sep 9, 2010·Cell Communication and Signaling : CCS·Lido Calorini, Francesca Bianchini
Nov 11, 2010·Journal of Orthopaedic Surgery and Research·Yoshihiro MatsumotoYukihide Iwamoto
Jul 15, 2006·BMC Musculoskeletal Disorders·Annina SipolaJuha Tuukkanen
Oct 31, 2003·Journal of Translational Medicine·Dimitrios PanutsopulosDemetrios A Spandidos
Feb 2, 2011·PloS One·Jun WeiAmy B Heimberger
Nov 16, 2006·PLoS Medicine·Atis MuehlenbachsPatrick E Duffy
Nov 7, 2006·Bone·Gilles BluteauJérôme Guicheux
Sep 18, 2007·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Manfred InfangerDaniela Grimm
Dec 7, 2005·Experimental Cell Research·Yin-Shan NgDavid T Shima
Jun 8, 2007·Blood Cells, Molecules & Diseases·Zaher K OtrockAli I Shamseddine
Feb 28, 2007·Critical Reviews in Oncology/hematology·Robert Roskoski
May 14, 2010·Biochimica Et Biophysica Acta·Shanchun GuoRuben R Gonzalez-Perez
Aug 18, 2005·Biochemical and Biophysical Research Communications·S E AldridgeM A Birch
Apr 28, 2005·The American Journal of Pathology·Shizuya SaikaAnita B Roberts
May 12, 2004·Fertility and Sterility·Ariadne Malamitsi-PuchnerBritt-Marie Landgren
Feb 24, 2009·Current Opinion in Cell Biology·Marja LohelaKari Alitalo
Nov 26, 2008·Clinics in Laboratory Medicine·Diana M GirnitaAdriana Zeevi
May 22, 2003·The American Journal of Pathology·Raffaella GiavazziMarco Presta

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.