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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Anti-FGFR4 antibodies and methods of use

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Mark S. Dennis¹, Luc Desnoyers¹, Dorothy French¹•Institutions (1)

Genentech¹

06 Apr 2012

24 citations

Journal Article•DOI•

Role of the fibroblast growth factor 19 in the skeletal system.

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Hao Chen¹, Jiazhou Li¹, Demao Zhang¹, Xuedong Zhou¹, Jing Xie¹ - Show less +1 more•Institutions (1)

Sichuan University¹

15 Jan 2021-Life Sciences

TL;DR: The background of FGF19 in bone is introduced, the research progress of F GF19 in the skeletal system is summarised, and the role and therapeutic potential are discussed in bone development and bone-related diseases.

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24 citations

Journal Article•DOI•

Growth Factor-Bearing Polymer Brushes - Versatile Bioactive Substrates Influencing Cell Response

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Evmorfia Psarra¹, Evmorfia Psarra², Elena Foster³, Ulla König¹, Jungmok You⁴, Yuichiro Ueda, Klaus Jochen Eichhorn¹, Martin Müller¹, Manfred Stamm², Manfred Stamm¹, Alexander Revzin³, Petra Uhlmann⁵, Petra Uhlmann¹ - Show less +9 more•Institutions (5)

Leibniz Association¹, Dresden University of Technology², University of California, Davis³, Kyung Hee University⁴, University of Nebraska–Lincoln⁵

16 Oct 2015-Biomacromolecules

TL;DR: The results illustrate that PAA brushes, particularly those biofunctionalized with chemisorbed GFs, produce an expected measurable effect on both cell types, and can be used as bioactive cell culture substrates with tuned efficiency.

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24 citations

Journal Article•DOI•

Role of Fibroblast Growth Factor Receptors in Astrocytic Stem Cells

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Alma Y. Galvez-Contreras¹, Rocio E. Gonzalez-Castaneda, Sonia Luquin, Oscar Gonzalez-Perez•Institutions (1)

University of Colima¹

01 Jan 2012-Current Signal Transduction Therapy

TL;DR: FGF2 is an important modulator of the cell fate of neural precursor and, promotes oligodendrogenesis in human brain and appears to be an important component in the anti-depressive effect of drugs.

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Abstract: There are two well-defined neurogenic regions in the adult brain, the subventricular zone (SVZ) lining the lateral wall of the lateral ventricles and, the subgranular zone (SGZ) in the dentate gyrus at the hippocampus. Within these neurogenic regions, there are neural stem cells with astrocytic characteristics, which actively respond to the basic fibroblast growth factor (bFGF, FGF2 or FGF-β) by increasing their proliferation, survival and differentiation, both in vivo and in vitro. FGF2 binds to fibroblast growth factor receptors 1 to 4 (FGFR1, FGFR2, FGFR3, FGFR4). Interestingly, these receptors are differentially expressed in neurogenic progenitors. During development, FGFR-1 and FGFR-2 drive oligodendrocytes and motor neuron specification. In particular, FGFR-1 determines oligodendroglial and neuronal cell fate, whereas FGFR-2 is related to oligodendrocyte specification. In the adult SVZ, FGF-2 promotes oligodendrogliogenesis and myelination. FGF-2 deficient mice show a reduction in the number of new neurons in the SGZ, which suggests that FGFR-1 is important for neuronal cell fate in the adult hippocampus. In human brain, FGF-2 appears to be an important component in the anti-depressive effect of drugs. In summary, FGF2 is an important modulator of the cell fate of neural precursor and, promotes oligodendrogenesis. In this review, we describe the expression pattern of FGFR2 and its role in neural precursors derived from the SVZ and the SGZ.

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24 citations

Journal Article•DOI•

Synergistic activity of fibronectin and fibroblast growth factor receptors on neuronal adhesion and neurite extension through extracellular signal-regulated kinase pathway

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Pill Hoon Choung¹, Byoung Moo Seo¹, Chong Pyoung Chung¹, Kenneth M. Yamada², Jun-Hyeog Jang¹ - Show less +1 more•Institutions (2)

New Generation University College¹, National Institutes of Health²

26 Jul 2002-Biochemical and Biophysical Research Communications

TL;DR: Findings indicate that FN-mediated signaling can collaborate with FGFRs signaling for neurite outgrowth through selective activation of ERK-type MAP kinase in PC12 cells, and suggest that FN and FGF act in concert to regulate cell differentiation in the nervous system.

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24 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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