Fibroblast growth factors, their receptors and signaling.

doi:10.1677/ERC.0.0070165

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Fibroblast growth factors, their receptors and signaling.

Journal Article•DOI•

Fibroblast growth factors, their receptors and signaling.

Ciaran Powers¹, S W McLeskey, Anton Wellstein¹•Institutions (1)

Georgetown University¹

01 Sep 2000-Endocrine-related Cancer (Bioscientifica Ltd)-Vol. 7, Iss: 3, pp 165-197

TL;DR: FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.

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Abstract: Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.

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Journal Article•DOI•

Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis.

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Wiebke Herzog¹, Carmen Sonntag¹, Sophia von der Hardt¹, Henry Roehl¹, Zoltán M. Varga², Matthias Hammerschmidt¹ - Show less +2 more•Institutions (2)

Max Planck Society¹, University of Freiburg²

01 Aug 2004-Development

TL;DR: The data suggest that Fgf3 signaling primarily promotes the transcriptional activation of genes regulating early specification steps of adenohypophyseal progenitor cells, which seems to be essential for the subsequent survival of pituitary cells, but not for pituitsary morphogenesis or pituitaries cell proliferation.

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Abstract: The pituitary gland consists of two major parts: the neurohypophysis, which is of neural origin; and the adenohypophysis, which is of non-neural ectodermal origin. Development of the adenohypophysis is governed by signaling proteins from the infundibulum, a ventral structure of the diencephalon that gives rise to the neurohypophysis. In mouse, the fibroblast growth factors Fgf8, Fgf10 and Fgf18 are thought to affect multiple processes of pituitary development: morphogenesis and patterning of the adenohypophyseal anlage; and survival, proliferation and differential specification of adenohypophyseal progenitor cells. Here, we investigate the role of Fgf3 during pituitary development in the zebrafish, analyzing lia/fgf3 null mutants. We show that Fgf3 signaling from the ventral diencephalon is required in a non-cell autonomous fashion to induce the expression of lim3, pit1 and other pituitary-specific genes in the underlying adenohypophyseal progenitor cells. Despite the absence of such early specification steps, fgf3 mutants continue to form a distinct pituitary anlage of normal size and shape, until adenohypophyseal cells die by apoptosis. We further show that Sonic Hedgehog (Shh) cannot rescue pituitary development, although it is able to induce adenohypophyseal cells in ectopic placodal regions of fgf3 mutants, indicating that Fgf3 does not act via Shh, and that Shh can act independently of Fgf3. In sum, our data suggest that Fgf3 signaling primarily promotes the transcriptional activation of genes regulating early specification steps of adenohypophyseal progenitor cells. This early specification seems to be essential for the subsequent survival of pituitary cells, but not for pituitary morphogenesis or pituitary cell proliferation.

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122 citations

Cites background from "Fibroblast growth factors, their re..."

...This results in a deletion of the last 79 amino acids of the protein, including 40 amino acids of the central core of 140 amino acids that is highly conserved among the different Fgf family members (Powers et al., 2000)....
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...Fgf3 and Fgf10 in mouse and zebrafish The different members of the family of Fgf ligands can be subgrouped according to sequence similarities and receptor specificities (Ornitz et al., 1996; Powers et al., 2000)....
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Journal Article•DOI•

FGF signaling is required for determination of otic neuroblasts in the chick embryo.

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Berta Alsina¹, Gina Abelló¹, Encarna Ulloa¹, Domingos Henrique², Cristina Pujades¹, Fernando Giraldez¹ - Show less +2 more•Institutions (2)

Pompeu Fabra University¹, Instituto de Medicina Molecular²

15 Mar 2004-Developmental Biology

TL;DR: It is suggested that FGF signaling in the otic epithelium is required for neuronal precursors to withdraw from cell division and irreversibly commit to neuronal fate.

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122 citations

Journal Article•DOI•

Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction.

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Leanne M. Cotton¹, Moira K O'Bryan², Barry T. Hinton¹•Institutions (2)

University of Virginia¹, Monash Institute of Medical Research²

15 Jan 2008-Endocrine Reviews

TL;DR: It is demonstrated that FGF/FGFR signaling is essential for normal epididymal function and prostate development and the involvement of the FGF signaling system in the regulation and maintenance of the male reproductive system is provided.

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Abstract: The major function of the reproductive system is to ensure the survival of the species by passing on hereditary traits from one generation to the next. This is accomplished through the production of gametes and the generation of hormones that function in the maturation and regulation of the reproductive system. It is well established that normal development and function of the male reproductive system is mediated by endocrine and paracrine signaling pathways. Fibroblast growth factors (FGFs), their receptors (FGFRs), and signaling cascades have been implicated in a diverse range of cellular processes including: proliferation, apoptosis, cell survival, chemotaxis, cell adhesion, motility, and differentiation. The maintenance and regulation of correct FGF signaling is evident from human and mouse genetic studies which demonstrate that mutations leading to disruption of FGF signaling cause a variety of developmental disorders including dominant skeletal diseases, infertility, and cancer. Over the course of this review, we will provide evidence for differential expression of FGFs/FGFRs in the testis, male germ cells, the epididymis, the seminal vesicle, and the prostate. We will show that this signaling cascade has an important role in sperm development and maturation. Furthermore, we will demonstrate that FGF/FGFR signaling is essential for normal epididymal function and prostate development. To this end, we will provide evidence for the involvement of the FGF signaling system in the regulation and maintenance of the male reproductive system.

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121 citations

Journal Article•DOI•

Structural and sequence motifs in dermatan sulfate for promoting fibroblast growth factor-2 (FGF-2) and FGF-7 activity.

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Kristen R. Taylor¹, Jennifer A. Rudisill¹, Richard L. Gallo¹•Institutions (1)

University of California, San Diego¹

18 Feb 2005-Journal of Biological Chemistry

TL;DR: Critical oligosaccharides are identified that promote specific members of the FGF family that are important for wound repair and angiogenesis.

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121 citations

Journal Article•DOI•

Endothelial cell integrins and COX-2: mediators and therapeutic targets of tumor angiogenesis.

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Curzio Rüegg¹, Olivier Dormond¹, Agnese Mariotti¹•Institutions (1)

University of Lausanne¹

04 Mar 2004-Biochimica et Biophysica Acta

TL;DR: The role of integrins and COX-2 in angiogenesis is reviewed, their cross talk is discussed, and implications relevant to their targeting to suppress tumorAngiogenesis are discussed.

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120 citations

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References

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Journal Article•DOI•

Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

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Avner Yayon¹, Michael Klagsbrun², Jeffrey D. Esko³, Philip Leder⁴, David M. Ornitz⁴ - Show less +1 more•Institutions (4)

Weizmann Institute of Science¹, Harvard University², University of Alabama at Birmingham³, Howard Hughes Medical Institute⁴

22 Feb 1991-Cell

TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.

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2,448 citations

Journal Article•DOI•

Protein modules and signalling networks

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Tony Pawson¹•Institutions (1)

Mount Sinai Hospital, Toronto¹

16 Feb 1995-Nature

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.

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Abstract: Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.

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2,433 citations

"Fibroblast growth factors, their re..." refers background in this paper

...One way these recruited target proteins may be localized to the activated receptor is through the interaction between their Src-homology 2 (SH2) domains and specific phosphotyrosine residues on the activated receptor (Pawson 1995)....
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...Phosphorylated tyrosine residues, in turn, recruit other signaling molecules to the activated receptors and propagate the signal through many possible transduction pathways (Pawson 1995)....
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Journal Article•DOI•

Thalidomide is an inhibitor of angiogenesis.

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Robert J. D'Amato¹, Michael S. Loughnan, Evelyn Flynn, Judah Folkman•Institutions (1)

Harvard University¹

26 Apr 1994-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.

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Abstract: Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.

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2,364 citations

Journal Article•DOI•

Receptor specificity of the fibroblast growth factor family.

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David M. Ornitz¹, Jingsong Xu¹, Jennifer S. Colvin¹, Donald G. McEwen¹, Craig A. MacArthur¹, François Coulier², Guangxia Gao³, Mitchell Goldfarb⁴ - Show less +4 more•Institutions (4)

Washington University in St. Louis¹, French Institute of Health and Medical Research², Columbia University³, Icahn School of Medicine at Mount Sinai⁴

21 Jun 1996-Journal of Biological Chemistry

TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.

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2,066 citations

"Fibroblast growth factors, their re..." refers background in this paper

...†From Ornitz et al. (1996), except where stated; ‡From Koga et al. (1995); §From Miralles et al. (1999); ¶From Xu et al. (1999). topologically identical to interleukin-1β (IL-1β) (Zhu et al. 1991), with which some members also share the feature of secretion by an endoplasmic reticulum…...
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...Mutation of all four cysteines to serines results in a protein with the same secondary structure and equally mitogenic for 3T3 cells as the wild-type FGF-2 (Foxet al. 1988), suggesting that the formation of disulfide bridges is not important for the secondary structure and mitogenic activity of…...
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...Ornitz et al. (1996) determined the specificity of different FGFs for different receptor isoforms by overexpressing these isoforms in Baf3 cells, which do not normally express FGFRs, and assaying for [3H]thymidine incorporation in these cells following treatment with different FGFs (see Table 2)....
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...1, IIIb 100 60 34 16 4 5 6 4 4 1, IIIc 100 104 0 102 59 55 0 1 21 2, IIIb 100 9 45 15 5 5 81 4 7 2, IIIc 100 64 4 94 25 61 2.5 16 89 3, IIIb 100 1 2 1 1 1 1 1 42 3, IIIc 100 107 1 69 12 9 1 41 96 4 100 113 6 108 7 79 2 76 75 Modified from Ornitz et al. (1996)....
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Journal Article•DOI•

The heparin-binding (fibroblast) growth factor family of proteins.

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Wilson H. Burgess, Thomas Maciag

01 Jan 1989-Annual Review of Biochemistry

1,994 citations

"Fibroblast growth factors, their re..." refers background in this paper

...Defining features of the FGF family are a strong affinity for heparin and HLGAGs (Burgess & Maciag 1989), as well as a central core of 140 amino acids that is highly homologous between different family members....
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