scholarly journals Fibroblast growth factors share binding sites in heparan sulphate

2005 ◽  
Vol 389 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Johan KREUGER ◽  
Per JEMTH ◽  
Emil SANDERS-LINDBERG ◽  
Liat ELIAHU ◽  
Dina RON ◽  
...  
Keyword(s):  
Growth Factors ◽  
Sequence Analysis ◽  
Binding Sites ◽  
Heparan Sulphate ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Cellular Targeting ◽  
Selective Modulation ◽  
Comprehensive Survey ◽  
Heparan Sulphate Proteoglycans

HS (heparan sulphate) proteoglycans bind secreted signalling proteins, including FGFs (fibroblast growth factors) through their HS side chains. Such chains contain a wealth of differentially sulphated saccharide epitopes. Whereas specific HS structures are commonly believed to modulate FGF-binding and activity, selective binding of defined HS epitopes to FGFs has generally not been demonstrated. In the present paper, we have identified a series of sulphated HS octasaccharide epitopes, derived from authentic HS or from biosynthetic libraries that bind with graded affinities to FGF4, FGF7 and FGF8b. These HS species, along with previously identified oligosaccharides that interact with FGF1 and FGF2, constitute the first comprehensive survey of FGF-binding HS epitopes based on carbohydrate sequence analysis. Unexpectedly, our results demonstrate that selective modulation of FGF activity cannot be explained in terms of binding of individual FGFs to specific HS target epitopes. Instead, different FGFs bind to identical HS epitopes with similar relative affinities and low selectivity, such that the strength of these interactions increases with increasing saccharide charge density. We conclude that FGFs show extensive sharing of binding sites in HS. This conclusion challenges the current notion of specificity in HS–FGF interactions, and instead suggests that a set of common HS motifs mediates cellular targeting of different FGFs.

Fibroblast growth factors and their receptors

1997 ◽  
Vol 75 (6) ◽  
pp. 669-685 ◽  
Author(s):  
Zoya Galzie ◽  
Anne R Kinsella ◽  
John A Smith
Keyword(s):  
Growth Factors ◽  
Heparan Sulphate ◽  
Fibroblast Growth Factors ◽  
Biological Properties ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Surface Receptors ◽  
Normal Tissues ◽  
Tumour Diagnosis ◽  
Heparan Sulphate Proteoglycans

Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens eliciting a wide variety of responses depending upon the target cell type. The knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. The complexity of the FGF family and the FGF-induced responses is reflected in the diversity and redundancy of the FGF receptors. In this review, a number of biochemical characteristics and biological properties of the FGF family and its receptors are described and their expression both in normal tissues and in tumours is discussed. Finally we speculate on the targetting of growth inhibition agents to tumours through FGF receptors. Key words: fibroblast growth factor, FGF receptor, heparan sulphate proteoglycans, tyrosine kinase receptors, FGF in tumour diagnosis.

scholarly journals Selectivity in glycosaminoglycan binding dictates the distribution and diffusion of fibroblast growth factors in the pericellular matrix

Open Biology ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 150277 ◽  
Author(s):  
Changye Sun ◽  
Marco Marcello ◽  
Yong Li ◽  
David Mason ◽  
Raphaël Lévy ◽  
...  
Keyword(s):  
Growth Factors ◽  
Binding Sites ◽  
Dermatan Sulfate ◽  
Fibroblast Growth Factors ◽  
Pericellular Matrix ◽  
Fibroblast Growth ◽  
Binding Properties ◽  
Protein Binding Sites ◽  
Biological Outcomes ◽  
And Diffusion

The range of biological outcomes generated by many signalling proteins in development and homeostasis is increased by their interactions with glycosaminoglycans, particularly heparan sulfate (HS). This interaction controls the localization and movement of these signalling proteins, but whether such control depends on the specificity of the interactions is not known. We used five fibroblast growth factors with an N-terminal HaloTag (Halo-FGFs) for fluorescent labelling, with well-characterized and distinct HS-binding properties, and measured their binding and diffusion in pericellular matrix of fixed rat mammary 27 fibroblasts. Halo-FGF1, Halo-FGF2 and Halo-FGF6 bound to HS, whereas Halo-FGF10 also interacted with chondroitin sulfate/dermatan sulfate, and FGF20 did not bind detectably. The distribution of bound FGFs in the pericellular matrix was not homogeneous, and for FGF10 exhibited striking clusters. Fluorescence recovery after photobleaching showed that FGF2 and FGF6 diffused faster, whereas FGF1 diffused more slowly, and FGF10 was immobile. The results demonstrate that the specificity of the interactions of proteins with glycosaminoglycans controls their binding and diffusion. Moreover, cells regulate the spatial distribution of different protein-binding sites in glycosaminoglycans independently of each other, implying that the extracellular matrix has long-range structure.

Structural and functional specificity of FGF receptors

1993 ◽  
Vol 340 (1293) ◽  
pp. 297-303 ◽  
Keyword(s):  
Growth Factors ◽  
Cell Surface ◽  
Tyrosine Kinase ◽  
Heparan Sulphate ◽  
Fibroblast Growth Factors ◽  
Binding Property ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Kinase Gene ◽  
Receptor System

Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens eliciting a wide variety of responses depending on the target cell type. The knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. Perhaps not surprisingly, the complexity of the FGF family and FGF induced responses is reflected in the diversity and redundancy of the FGF receptors. The molecular cloning of the signal transducing receptors for fibroblast growth factors has revealed a tyrosine kinase gene family with at least four members. Differential splicing and polyadenylation creates further diversity in the FGF receptor system. These numerous receptor forms have both distinct and redundant properties. We are only now beginning to understand how the different receptors are activated by the various FGFs and how they are expressed by various cells and tissues. FGF binding to the tyrosine kinase receptors needs the assistance of heparan sulphate side chains of proteoglycans present at the cell surface and in the extracellular matrix. As several other growth factors share the heparin binding property of FGFs, the dual receptor system for FGFs might be an example of a more widely used principle.

scholarly journals Sequence Analysis of Heparan Sulfate Epitopes with Graded Affinities for Fibroblast Growth Factors 1 and 2

2001 ◽  
Vol 276 (33) ◽  
pp. 30744-30752 ◽  
Author(s):  
Johan Kreuger ◽  
Markku Salmivirta ◽  
Luisa Sturiale ◽  
Guillermo Giménez-Gallego ◽  
Ulf Lindahl
Keyword(s):  
Growth Factors ◽  
Sequence Analysis ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth

Cytogenetics, Immunostaining for Fibroblast Growth Factors, p53 Sequencing, and Clinical Features of Two Cases of Cystosarcoma Phyllodes

2000 ◽  
Vol 5 (3) ◽  
pp. 179-190 ◽  
Author(s):  
PAUL V. WOOLLEY ◽  
SUSANNE M. GOLLIN ◽  
WAHEEB RISKALLA ◽  
SYDNEY FINKELSTEIN ◽  
DAVID F. STEFANIK ◽  
...  
Keyword(s):  
Growth Factors ◽  
Clinical Features ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Cystosarcoma Phyllodes

Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications

2019 ◽  
Vol 20 (8) ◽  
pp. 852-870
Author(s):  
Hassan Dianat-Moghadam ◽  
Ladan Teimoori-Toolabi
Keyword(s):  
Growth Factors ◽  
Wound Repair ◽  
Fibroblast Growth Factors ◽  
Predictive Biomarkers ◽  
Fibroblast Growth ◽  
Loss Of Function ◽  
Cellular Processes ◽  
Fgfr Signaling ◽  
Proliferation And Metastasis ◽  
Immense Potential

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor–stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored.

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