DISTINCT ROLE OF 2-O-SULFATE, N-SULFATE, AND 6-O-SULFATE GROUPS OF HEPARIN IN THE FORMATION OF THE TERNARY COMPLEX WITH BASIC FIBROBLAST GROWTH-FACTOR AND SOLUBLE FGF RECEPTOR-1

Citation
M. Rusnati et al., DISTINCT ROLE OF 2-O-SULFATE, N-SULFATE, AND 6-O-SULFATE GROUPS OF HEPARIN IN THE FORMATION OF THE TERNARY COMPLEX WITH BASIC FIBROBLAST GROWTH-FACTOR AND SOLUBLE FGF RECEPTOR-1, Biochemical and biophysical research communications, 203(1), 1994, pp. 450-458
Citations number
33
Categorie Soggetti
Biology,Biophysics
ISSN journal
0006291X
Volume
203
Issue
1
Year of publication
1994
Pages
450 - 458
Database
ISI
SICI code
0006-291X(1994)203:1<450:DRO2NA>2.0.ZU;2-K
Abstract
Interaction of basic fibroblast growth factor (bFGF) with heparan sulf ate proteoglycans (HSPGs) plays an important role in the binding of bF GF to its tyrosine kinase receptor (FGFR). The molecular bases of this interaction were investigated by evaluating the capacity of conventio nal and selectively desulfated heparins i) to affect the binding of bF GF to FGFR and HSPGs of NIH 3T3 cells transfected with FGFR-1/flg cDNA , ii) to facilitate the interaction of bFGF with a recombinant soluble form of the extracellular domain of FGFR-1/flg (xcFGFR-1), and iii) t o protect xcFGFR-1 from tryptic cleavage. 6-O-desulfated (6-O-DS) hepa rin, but not 2-O-desulfated (2-O-DS) and N-desulfated/N-acetylated (N- DS/N-Ac) heparins, retains the capacity to bind bFGF, as assessed by i ts ability to inhibit bFGF-binding to cell-associated FGFR-1 and HSPGs . On the other hand, at variance with conventional heparin, 2-O-DS, N- DS/N-Ac, and 6-O-DS heparins are all ineffective in potentiating the b inding of bFGF to xcFGFR-1 and protecting xcFGFR-1 from tryptic cleava ge. The data indicate that 6-O-sulfate groups are not essential for th e interaction of heparin with bFGF but are involved in the interaction with xcFGFR-1. Our findings support the hypothesis that HSPGs modulat e the binding of bFGF to FGFR through the formation of a ternary compl ex in which the glycosaminoglycan chains interact with bFGF via 2-O- a nd N-sulfate groups and with FGFR also via 6-O-sulfate groups. (C) 199 4 Academic Press, Inc.