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 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.

scholarly journals Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Sung-Ho Huh ◽  
Mark E Warchol ◽  
David M Ornitz
Keyword(s):  
Growth Factors ◽  
Hair Cells ◽  
Fibroblast Growth Factors ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Feedback Mechanism ◽  
Outer Hair Cells ◽  
Fibroblast Growth ◽  
Supporting Cells ◽  
Fgf Receptor

The sensory and supporting cells (SCs) of the organ of Corti are derived from a limited number of progenitors. The mechanisms that regulate the number of sensory progenitors are not known. Here, we show that Fibroblast Growth Factors (FGF) 9 and 20, which are expressed in the non-sensory (Fgf9) and sensory (Fgf20) epithelium during otic development, regulate the number of cochlear progenitors. We further demonstrate that Fgf receptor (Fgfr) 1 signaling within the developing sensory epithelium is required for the differentiation of outer hair cells and SCs, while mesenchymal FGFRs regulate the size of the sensory progenitor population and the overall cochlear length. In addition, ectopic FGFR activation in mesenchyme was sufficient to increase sensory progenitor proliferation and cochlear length. These data define a feedback mechanism, originating from epithelial FGF ligands and mediated through periotic mesenchyme that controls the number of sensory progenitors and the length of the cochlea.

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.

Expression of Fibroblast Growth Factors (FGF) and FGF Receptor (FGFR) in the Horse Placenta

2005 ◽  
Vol 34 (s1) ◽  
pp. 39-40
Author(s):  
C. Pfarrer ◽  
M. Abd-Elnaeim ◽  
W. R. Allen ◽  
S. Wilsher ◽  
D. Schams ◽  
...  
Keyword(s):  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Fgf Receptor

Diverse forms of a receptor for acidic and basic fibroblast growth factors

1990 ◽  
Vol 10 (9) ◽  
pp. 4728-4736
Author(s):  
D E Johnson ◽  
P L Lee ◽  
J Lu ◽  
L T Williams
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factors ◽  
Cdna Clones ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Basic Fgf ◽  
Extracellular Region ◽  
Membrane Spanning

We recently reported the isolation of a chicken cDNA clone encoding a basic fibroblast growth factor (FGF) receptor that has three immunoglobulinlike domains in the extracellular region. We have now identified four unique human cDNA clones encoding previously unknown FGF receptor variants which contain only two immunoglobulinlike domains. Two of the human clones encode membrane-spanning receptors, and two encode putative secreted forms. Both the three- and two-immunoglobulinlike-domain forms mediate biological responsiveness to acidic and basic FGF. Thus, the first immunoglobulinlike domain of the three-domain form may have a function other than binding of acidic and basic FGF.

scholarly journals Diverse forms of a receptor for acidic and basic fibroblast growth factors.

1990 ◽  
Vol 10 (9) ◽  
pp. 4728-4736 ◽  
Author(s):  
D E Johnson ◽  
P L Lee ◽  
J Lu ◽  
L T Williams
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factors ◽  
Cdna Clones ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Basic Fgf ◽  
Extracellular Region ◽  
Membrane Spanning

We recently reported the isolation of a chicken cDNA clone encoding a basic fibroblast growth factor (FGF) receptor that has three immunoglobulinlike domains in the extracellular region. We have now identified four unique human cDNA clones encoding previously unknown FGF receptor variants which contain only two immunoglobulinlike domains. Two of the human clones encode membrane-spanning receptors, and two encode putative secreted forms. Both the three- and two-immunoglobulinlike-domain forms mediate biological responsiveness to acidic and basic FGF. Thus, the first immunoglobulinlike domain of the three-domain form may have a function other than binding of acidic and basic FGF.

scholarly journals The role of fibroblast growth factors and their receptors in prostate cancer

2004 ◽  
Vol 11 (4) ◽  
pp. 709-724 ◽  
Author(s):  
B Kwabi-Addo ◽  
M Ozen ◽  
M Ittmann
Keyword(s):  
Prostate Cancer ◽  
Growth Factors ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Prostate Cancer Progression ◽  
Fgf Receptor

Prostate cancer is the most common malignancy in men in the USA and the second leading cause of cancer deaths. Fibroblast growth factors (FGFs), including FGF1 (acidic FGF), FGF2 (basic FGF), FGF6 and FGF8 are all expressed at increased levels in prostate cancer as paracrine and/or autocrine growth factors for the prostate cancer cells. In addition, increased mobilization of FGFs from the extracellular matrix in cancer tissues can increase the availability of FGFs to cancer cells. Prostate cancer epithelial cells express all four types of FGF receptors (FGFR-1 to -4) at variable frequencies. Expression of FGFR-1 and FGFR-4 is most closely linked to prostate cancer progression, while the role of FGFR-2 remains controversial. Activation of FGF receptors can activate multiple signal transduction pathways including the phospholipase Cγ, phosphatidyl inositol 3-kinase, mitogen-activated protein kinase and signal transducers and activators of transcription (STAT) pathways, all of which play a role in prostate cancer progression. Sprouty proteins can negatively regulate FGF signal transduction, potentially limiting the impact of FGF signaling in prostate cancer, but in a significant fraction of prostate cancers there is decreased expression of Sprouty1 mRNA and protein. The effects of increased FGF receptor signaling are wide ranging and involve both the cancer cells and surrounding stroma, including the vasculature. The net result of increased FGF signaling includes enhanced proliferation, resistance to cell death, increased motility and invasiveness, increased angiogenesis, enhanced metastasis, resistance to chemotherapy and radiation and androgen independence, all of which can enhance tumor progression and clinical aggressiveness. For this reason, the FGF signaling system it is an attractive therapeutic target, particularly since therapies targeting FGF receptors and/or FGF signaling can affect both the tumor cells directly and tumor angiogenesis. A number of approaches that could target FGF receptors and/or FGF receptor signaling in prostate cancer are currently being developed.

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