Ability of different chemically modified heparins to potentiate the biological activity of heparin-binding growth factor 1. Lack of correlation with growth factor binding

Biochemistry ◽  
1992 ◽  
Vol 31 (28) ◽  
pp. 6498-6503 ◽  
Author(s):  
David A. Belford ◽  
Ian A. Hendry ◽  
Christopher R. Parish
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Chemically Modified

scholarly journals The Heparin-binding Domain of IGFBP-2 Has Insulin-like Growth Factor Binding-independent Biologic Activity in the Growing Skeleton

2011 ◽  
Vol 286 (16) ◽  
pp. 14670-14680 ◽  
Author(s):  
Masanobu Kawai ◽  
Anne C. Breggia ◽  
Victoria E. DeMambro ◽  
Xinchun Shen ◽  
Ernesto Canalis ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Domain ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Biologic Activity ◽  
Heparin Binding Domain

Mutations in the heparin-binding domains of human basic fibroblast growth factor alter its biological activity

Biochemistry ◽  
1991 ◽  
Vol 30 (22) ◽  
pp. 5608-5615 ◽  
Author(s):  
William F. Heath ◽  
Amanda S. Cantrell ◽  
Nancy G. Mayne ◽  
S. Richard Jaskunas
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Binding Domains

scholarly journals Oligomeric self-association of basic fibroblast growth factor in the absence of heparin-like glycosaminoglycans

1999 ◽  
Vol 341 (3) ◽  
pp. 613-620 ◽  
Author(s):  
Joseph C. DAVIS ◽  
Ganesh VENKATARAMAN ◽  
Zachary SHRIVER ◽  
P. Antony RAJ ◽  
Ram SASISEKHARAN
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Fgf Receptor ◽  
Natural Tendency ◽  
Heparin Binding Growth Factors ◽  
Self Association

Basic fibroblast growth factor (FGF-2) represents a class of heparin-binding growth factors that are stored in the extracellular matrix attached to heparin-like glycosaminoglycans (HLGAGs). It has been proposed that cell surface HLGAGs have a central role in the biological activity of FGF-2, presumably by inducing dimers or oligomers of FGF-2 and leading to the dimerization or oligomerization of FGF receptor and hence signal transduction. We have previously proposed that FGF-2 possesses a natural tendency to self-associate to form FGF-2 dimers and oligomers; HLGAGs would enhance FGF-2 self-association. Here, through a combination of spectroscopic, chemical cross-linking and spectrometric techniques, we provide direct evidence for the self-association of FGF-2 in the absence of HLGAGs, defying the notion that HLGAGs induce FGF-2 oligomerization. Further, the addition of HLGAGs seems to enhance significantly the FGF-2 oligomerization process without affecting the relative percentages of FGF-2 dimers, trimers or oligomers. FGF-2 self-association is consistent with FGF-2's possessing biological activity both in the presence and in the absence of HLGAGs; this leads us to propose that FGF-2 self-association enables FGF-2 to signal both in the presence and in the absence of HLGAGs.

scholarly journals Cleavage of K-FGF produces a truncated molecule with increased biological activity and receptor binding affinity.

1993 ◽  
Vol 121 (3) ◽  
pp. 705-713 ◽  
Author(s):  
P Bellosta ◽  
D Talarico ◽  
D Rogers ◽  
C Basilico
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Growth Factor ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Biologically Active ◽  
Heparin Binding ◽  
Wild Type ◽  
Mammalian Expression

The K-FGF/HST (FGF-4) growth factor is a member of the FGF family which is efficiently secreted and contains a single N-linked glycosylation signal. To study the role of glycosylation in the secretion of K-FGF, we mutated the human K-fgf cDNA to eliminate the glycosylation signal and the mutated cDNA was cloned into a mammalian expression vector. Studies of immunoprecipitation from the conditioned medium of cells expressing this plasmid revealed that the lack of glycosylation did not impair secretion, however the unglycosylated protein was immediately cleaved into two NH2-terminally truncated peptides of 13 and 15 kD, which appeared to be more biologically active than the wild-type protein. These two proteins also showed higher heparin binding affinity than that of wt K-FGF. We have expressed in bacteria the larger of these two proteins (K140), in which the NH2-terminal 36 amino acids present in the mature form of K-FGF have been deleted. Mitogenicity assays on several cell lines showed that purified recombinant K140 had approximately five times higher biological activity than wild-type recombinant K-FGF. Studies of receptor binding showed that K140 had higher affinity than wt K-FGF for two of the four members of FGF receptor's family, specifically for FGFR-1 (flg) and FGFR-2 (bek). K140 also had increased heparin binding ability, but this property does not appear to be responsible for the increased affinity for FGF receptors. Thus removal of the NH2-terminal 36 amino acids from the mature K-FGF produces growth factor molecules with an altered conformation, resulting in higher heparin affinity, and more efficient binding to FGF receptors. Although it is not clear whether cleavage of K-FGF to generate K140 occurs in vivo, this could represent a novel mechanism of modulation of growth factor activity.

Structure, Dynamics and Heparin Binding of the C-terminal Domain of Insulin-like Growth Factor-binding Protein-2 (IGFBP-2)

2006 ◽  
Vol 364 (4) ◽  
pp. 690-704 ◽  
Author(s):  
Zhihe Kuang ◽  
Shenggen Yao ◽  
David W. Keizer ◽  
Chunxiao C. Wang ◽  
Leon A. Bach ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Factor Binding ◽  
Structure Dynamics ◽  
Terminal Domain
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