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•

Delineating the angiogenic gene expression profile before pulmonary vascular remodeling in a lamb model of congenital heart disease

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Jing Tian, Sohrab Fratz¹, Yali Hou, Qing Lu, Agnes Görlach¹, John Hess¹, Christian Schreiber², Sanjeev A. Datar³, Peter Oishi³, John Nechtman⁴, Robert H. Podolsky⁴, Jin-Xiong She⁴, Jeffrey R. Fineman³, Stephen M. Black - Show less +10 more•Institutions (4)

Technische Universität München¹, Ludwig Maximilian University of Munich², University of California, San Francisco³, Georgia Regents University⁴

01 Jan 2011-Physiological Genomics

TL;DR: A "proangiogenic" gene expression profile in a lamb model of CHD with increased PBF that precedes onset of pulmonary vascular remodeling is identified and FGF2, Angpt2, Birc5, and ccl2 may play important roles in the angiogenic response.

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Abstract: Disordered angiogenesis is implicated in pulmonary vascular remodeling secondary to congenital heart diseases (CHD). However, the underlying genes are not well delineated. We showed previously that...

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19 citations

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

...family of the heparin-binding FGF growth factors (47, 48)....
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Journal Article•DOI•

Enhanced efficacy in anti-tumour activity by combined therapy of recombinant FGFR-1 related angiogenesis and low-dose cytotoxic agent

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S.P. Zheng¹, S.J. Zheng¹, R.L. Wu¹, F.Y. Huang, L.M. Cao¹, C.L. Jiao - Show less +2 more•Institutions (1)

Tongji Medical College¹

01 Sep 2007-European Journal of Cancer

TL;DR: The idea that the cFR-1 vaccine and low-dose gemcitabine combination strategy synergistically strengthens anti-tumour activity via suppression of tumour angiogenesis without overt toxicity in tumour-bearing mice is supported.

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19 citations

Patent•

Modified clostridial toxins with enhanced translocation capability and enhanced targeting activity

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Lance E. Steward¹, Joseph Francis¹, Ester Fernandez-Salas¹, Marcella A. Gilmore¹, Shengwen Li¹, Kei Roger Aoki¹ - Show less +2 more•Institutions (1)

Allergan¹

10 Jul 2007

TL;DR: In this paper, the authors describe modified Clostridial toxins comprising a Clostrichial toxin enzymatic domain, an enhanced targeting domain and a translocation facilitating domain.

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Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain, a translocation facilitating domain and an enhanced targeting domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.

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19 citations

Journal Article•DOI•

SNT1/FRS2 mediates germinal vesicle breakdown induced by an activated FGF receptor1 in Xenopus oocytes.

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Kathleen Mood¹, Robert Friesel¹, Ira O. Daar¹•Institutions (1)

National Institutes of Health¹

06 Sep 2002-Journal of Biological Chemistry

TL;DR: It is shown that the Xenopus homolog of mammalian FRS-2 (XFRS2) is essential for the induction of oocyte maturation by an XFG FR1 harboring an activating mutation (XFGFR1act), and that Mek/MAPK activity is critical forThe induction and/or maintenance of H1 kinase activity at metaphase of meiosis II in progesterone-treated oocytes.

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19 citations

Journal Article•DOI•

Novel insights into the role of hypoxia‑inducible factor‑1 in the pathogenesis of human post‑intubation tracheal stenosis

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Zhi-Gang Cai¹, Haitao Li¹, Hefang Zhang¹, Shuo Han¹, Rui-Jin An¹, Xixin Yan¹ - Show less +2 more•Institutions (1)

Hebei Medical University¹

01 Sep 2013-Molecular Medicine Reports

TL;DR: HIF-1α is involved in the pathogenesis of PTS and may be a potential key regulator in the initiation and facilitation of this process.

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Abstract: Hypoxia is an important mechanism involved in dermal scar formation. Post-intubation tracheal stenosis (PTS) has similar pathological characteristics and formation mechanisms to skin hypertrophic scars. Hypoxia-inducible factor‑1α (HIF‑1α) is a nuclear transcription factor that facilitates the adaptation of human cells to compromised oxygen tension under hypoxic conditions. The aim of this study was to investigate whether hypoxia and HIF-1α were involved in PTS. In the first part of our study, we observed the effects of tracheal mucosal pressure exerted by the endotracheal tube cuff and duration of intubation on tracheal stenosis using prospective methods. In the second part of our study, 24 patients were divided into three groups, according to the characteristics observed using bronchoscopy: granulation phase group, proliferative phase group and mature phase group. Tissues showing dysplasia were obtained using bronchoscopy forceps, and western blotting was performed to detect the protein expression of HIF-1α and its target genes, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β. In experiment one, we observed that the tracheal mucosal pressure exerted by the endotracheal tube cuff in the PTS group was significantly higher compared with that in the group without PTS, and the duration of intubation was longer compared with that in the group without PTS (P<0.05). In experiment two, we observed that the expression of HIF-1α was highest in the granulation phase, showed a decrease in the proliferative phase and in the mature phase was significantly reduced compared with the other two phases. The results were similar for VEGF and bFGF. TGF‑β protein expression was highest in the proliferative phase, significantly reduced in the mature phase and the same trends were observed for collagen type Ⅰ and III, and α-smooth muscle actin. HIF-1α is involved in the pathogenesis of PTS and may be a potential key regulator in the initiation and facilitation of this process.

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19 citations

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

...Basic FGF, a member of the fibroblast growth factor family, has been confirmed by an increasing number of studies to promote wound healing by increasing fibroblast migration, proliferation and angiogenic function, and in particular, to play a role in granulation tissue formation (29-31)....
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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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