Structure-function relationship of basic fibroblast growth factor: Site-directed mutagenesis of a putative heparin-binding and receptor-binding region

1992 ◽  
Vol 185 (3) ◽  
pp. 1098-1107 ◽  
Author(s):  
M. Presta ◽  
M. Statuto ◽  
A. Isacchi ◽  
P. Caccia ◽  
A. Pozzi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Binding Region ◽  
Function Relationship ◽  
Relationship Of ◽  
Receptor Binding Region

scholarly journals Possible dissociation of the heparin-binding and mitogenic activities of heparin-binding (acidic fibroblast) growth factor-1 from its receptor-binding activities by site-directed mutagenesis of a single lysine residue.

1990 ◽  
Vol 111 (5) ◽  
pp. 2129-2138 ◽  
Author(s):  
W H Burgess ◽  
A M Shaheen ◽  
M Ravera ◽  
M Jaye ◽  
P J Donohue ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Glutamic Acid ◽  
Mitogenic Activity ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Wild Type ◽  
Acidic Fibroblast Growth Factor

The fibroblast or heparin-binding growth factors (HBGFs) are thought to be modulators of cell growth and migration, angiogenesis, wound repair, neurite extension, and mesoderm induction. A better understanding of the structural basis for the different activities of these proteins should facilitate the development of agonists and antagonists of specific HBGF activities and identification of the signal transduction pathways involved in the mechanisms of action of these growth factors. Chemical modification studies of Harper and Lobb (Harper, J. W., and R. R. Lobb. 1988. Biochemistry. 27:671-678) implicated lysine 132 in HBGF-1 (acidic fibroblast growth factor) as being important to the heparin-binding, receptor-binding, and mitogenic activities of the protein. We changed lysine 132 to a glutamic acid residue by site-directed mutagenesis of the human cDNA and expressed the mutant protein in Escherichia coli to obtain sufficient quantities for functional studies. Replacement of this lysine with glutamic acid reduces the apparent affinity of HBGF-1 for immobilized heparin (elutes at 0.45 M NaCl vs. 1.1 M NaCl for wild-type). Mitogenic assays established two points: (a) human recombinant HBGF-1 is highly dependent on the presence of heparin for optimal mitogenic activity, and (b) the change of lysine 132 to glutamic acid drastically reduces the specific mitogenic activity of HBGF-1. The poor mitogenic activity of the mutant protein does not appear to be due to a reduced affinity for the HBGF receptor. Similarly, the mutant HBGF-1 can stimulate tyrosine kinase activity and induce protooncogene expression. Differences in the biological properties of the wild-type and mutant proteins were observed in transfection studies. Mutant HBGF-1 expression in transfected NIH 3T3 cells did not induce the same transformed phenotype characteristic of cells expressing wild-type HBGF-1. Together these data indicate that different functional properties of HBGF-1 may be dissociated at the structural level.

scholarly journals Decoding the Genetic Alterations in Genes of Fibroblast Growth Factor Family and Their Possible Association with HNSCC

2021 ◽  
pp. 698-710
Author(s):  
A. Akshaya ◽  
J. Vijayashree Priyadharsini ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
Nidhi Poddar
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Demographic Data ◽  
Primary Tumour ◽  
Genetic Alterations ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Fibroblast Growth Factor Family ◽  
Significant Difference ◽  
Cancer Phenotypes

Introduction: HNSCC is a type of cancer in the oral and pharynx region. Several mutations/variations are observed in these cancer phenotypes. Fibroblast growth factor belongs to the family of heparin binding growth factors. FGFs are multifunctional proteins with a wide variety of effects; they are most commonly mitogens. Their expression pattern correlates with invasion of HNSCC. Aim: To assess the genetic alterations in genes of the fibroblast growth factor family and their association with HNSCC. Materials and Methods: The demographic data and samples of 528 HNSCC patients was collected from the cBioportal database. Oncoprint analysis was done to assess the amplification and genetic alterations of the members of the FGF gene family. String analysis was performed to evaluate the protein-protein interaction. The information about previous reported mutation and correlation with novel and reported mutation was obtained using GnomAD analysis. Results and Discussion: FGF3,4 and 19 genes showed maximum variation (25%). FGF4 and FGF19 genes showed maximum amplification in addition to deletion mutation. Excitingly FGF3, FGF4 and FGF19 genes showed similar amplification patterns in most of the HNSCC patients. Statistical significant difference in the gene expression of FGF3 9.578 x 10-3 observed between normal and primary tumour. S.  Findings showed many novel mutations and also 4 reported mutations ie:FGF1, FGF12, FGF20, FGF21 Conclusion: Our present study concludes that more evidence is required to confirm their association with HNSCC.

scholarly journals Identification of a fibroblast growth factor-binding protein in Drosophila melanogaster.

1991 ◽  
Vol 11 (4) ◽  
pp. 2319-2323 ◽  
Author(s):  
J S Doctor ◽  
F M Hoffmann ◽  
B B Olwin
Keyword(s):  
Molecular Weight ◽  
Drosophila Melanogaster ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Binding Proteins ◽  
Specific Binding ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Acidic Fibroblast Growth Factor ◽  
Heparin Binding Growth Factors

As assessed by competitive binding and protein-crosslinking experiments, Drosophila melanogaster cells possess basic fibroblast growth factor (bFGF)-specific binding proteins that are similar to FGF receptors on vertebrate cells in molecular weight and binding affinity; these D. melanogaster cells, however, have no detectable binding proteins for acidic fibroblast growth factor (aFGF). Consistent with the presence of bFGF-specific binding proteins, D. melanogaster cells degrade bFGF but not aFGF. These results indicate the conservation of heparin-binding growth factors and receptors between vertebrates and D. melanogaster.

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