VEGF(121), the 121-amino acid form of vascular endothelial growth factor is a homodimer with nine cysteine residues per monomer. While three intramolecular and two intermolecular disulfide bonds have been mapped, the state of the ninth cysteine, Cys116, is not known. In this study, we determined that human VEGF(121) contains a third interchain disulfide bond between Cys116 of each monomer. We also isolated a VEGF(121) variant with two extra cysteines bound to each Cys116. No evidence was found for the exsistence of Cys116 in the reduced state. In fact, selective reduction of the Cys116 interchain disulfide bond yielded an unstable VEGF(121) molecule, which reoxidized quickly. Biological activities of VEGF(121) Cys116 variants were assessed. The oxidative state of Cys116 has no effect on binding or proliferation activities but may be important for overall stability of the molecule.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0003-9861(02)00239-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Use of mendelian randomization to assess the causal associations of circulating plasma proteins with 12-lead ECG parameters.
Int Immunopharmacol
December 2024
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, 150086, Xuefu Road 246, Harbin, Province Heilongjiang, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, 150086, Xuefu Road 246, Harbin, Province Heilongjiang, China; Heilongjiang Provincial Key Laboratory of Panvascular Disease, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, Province Heilongjiang, China. Electronic address:
Article Synopsis
- The study aimed to explore the relationship between plasma proteins and various electrocardiogram (ECG) traits to enhance understanding of cardiac conduction and its implications for arrhythmias.
- Researchers utilized a Mendelian randomization approach to identify specific proteins linked to ECG traits such as P wave duration, PR interval, and others, confirming their findings through several analytical methods.
- The analysis revealed several proteins associated with different ECG attributes, and some were identified as potential drug targets, indicating that these proteins may play a role in managing cardiac conduction disorders.
Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2.
Cell Commun Signal
April 2024
Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
The endothelial glycocalyx, located at the luminal surface of the endothelium, plays an important role in the regulation of leukocyte adhesion, vascular permeability, and vascular homeostasis. Endomucin (EMCN), a component of the endothelial glycocalyx, is a mucin-like transmembrane glycoprotein selectively expressed by venous and capillary endothelium. We have previously shown that knockdown of EMCN impairs retinal vascular development in vivo and vascular endothelial growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, and tube formation by human retinal endothelial cells in vitro and that EMCN is essential for VEGF165-stimulated clathrin-mediated endocytosis and signaling of VEGF receptor 2 (VEGFR2).
View Article and Find Full Text PDFMolecularly Imprinted Nanomedicine for Anti-angiogenic Cancer Therapy via Blocking Vascular Endothelial Growth Factor Signaling.
Nano Lett
September 2023
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
The VEGF-VEGFR2 (VEGF = vascular endothelial growth factor) signaling has been a promising target in cancer therapy. However, because conventional anti-angiogenic therapeutics suffer from drawbacks, particularly severe side effects, novel anti-angiogenic strategies are much needed. Herein, we report the rational engineering of VEGF-targeted molecularly imprinted polymer nanoparticles (nanoMIP) for anti-angiogenic cancer therapy.
View Article and Find Full Text PDFObjective: The aim of this study is to determine biomarkers, which may be used in order to understand the pathophysiology, the diagnosis, progression surveillance/monitoring, and treatment efficacy of high graded glial tumors.
Background: Radiological imaging in the diagnosis and relapse surveillance of glial tumors is sometimes insufficient. There is need for additional methods of diagnosis and surveillance in order to rule out contradictory circumstances.
ERO1 alpha deficiency impairs angiogenesis by increasing N-glycosylation of a proangiogenic VEGFA.
Redox Biol
October 2022
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy. Electronic address:
N-glycosylation and disulfide bond formation are two essential steps in protein folding that occur in the endoplasmic reticulum (ER) and reciprocally influence each other. Here, to analyze crosstalk between N-glycosylation and oxidation, we investigated how the protein disulfide oxidase ERO1-alpha affects glycosylation of the angiogenic VEGF, a key regulator of vascular homeostasis. ERO1 deficiency, while retarding disulfide bond formation in VEGF, increased utilization of its single N-glycosylation sequon, which lies close to an intra-polypeptide disulfide bridge, and concomitantly slowed its secretion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!