Investigating the effect of VEGF glycosylation on glycosaminoglycan binding and protein unfolding

被引:30
作者
Brandner, B
Kurkela, R
Vihko, P
Kungl, AJ [1 ]
机构
[1] Graz Univ, Inst Pharmaceut Sci, A-8010 Graz, Austria
[2] Oulu Univ, Bioctr Oulu, FIN-90014 Oulu, Finland
关键词
growth factor; heparin; heparan sulfate;
D O I
10.1016/j.bbrc.2005.12.079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
VEGF(165) binding to endothelial cells is potentiated by glycosaminoglycans (GAGs). Here, we have investigated the impact of VEGF(165) N-glycosylation on GAG binding. Although glycosylated VEGF(165) bound to heparin with only slightly higher affinity than non-glycosylated VEGF(165), the natural ligand heparan sulfate induced a conformational change only in the glycosylated protein. Unfolding studies of the VEGF proteins indicated a stabilising effect of heparin on the growth factor structure. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:836 / 839
页数:4
相关论文
共 29 条
[1]   Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development [J].
Brickman, YG ;
Ford, MD ;
Gallagher, JT ;
Nurcombe, V ;
Bartlett, PF ;
Turnbull, JE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (08) :4350-4359
[2]   STRUCTURAL REQUIREMENTS FOR DIMERIZATION, GLYCOSYLATION, SECRETION, AND BIOLOGICAL FUNCTION OF VPF/VEGF [J].
CLAFFEY, KP ;
SENGER, DR ;
SPIEGELMAN, BM .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1995, 1246 (01) :1-9
[3]   VEGF(121), A VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) ISOFORM LACKING HEPARIN-BINDING ABILITY, REQUIRES CELL-SURFACE HEPARAN SULFATES FOR EFFICIENT BINDING TO THE VEGF RECEPTORS OF HUMAN-MELANOMA CELLS [J].
COHEN, T ;
GITAYGOREN, H ;
SHARON, R ;
SHIBUYA, M ;
HALABAN, R ;
LEVI, BZ ;
NEUFELD, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (19) :11322-11326
[4]   High Levels of Biologically Active Vascular Endothelial Growth Factor (VEGF) are Produced by the Baculovirus Expression System [J].
Cohen, Tzafra ;
Gitay-Goren, Hela ;
Neufeld, Gem ;
Levi, Ben-Zion .
GROWTH FACTORS, 1992, 7 (02) :131-138
[5]   THE FMS-LIKE TYROSINE KINASE, A RECEPTOR FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR [J].
DEVRIES, C ;
ESCOBEDO, JA ;
UENO, H ;
HOUCK, K ;
FERRARA, N ;
WILLIAMS, LT .
SCIENCE, 1992, 255 (5047) :989-991
[6]   The biology of vascular endothelial growth factor [J].
Ferrara, N ;
DavisSmyth, T .
ENDOCRINE REVIEWS, 1997, 18 (01) :4-25
[7]  
Ferrara N, 2000, RECENT PROG HORM RES, V55, P15
[8]   Age-dependent modulation of heparan sulfate structure and function [J].
Feyzi, E ;
Saldeen, T ;
Larsson, E ;
Lindahl, U ;
Salmivirta, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (22) :13395-13398
[9]  
Fuh G, 2000, J BIOL CHEM, V275, P26690
[10]  
GITAYGOREN H, 1992, J BIOL CHEM, V267, P6093