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•

Extrinsic regulation of cardiomyocyte differentiation of embryonic stem cells.

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Kang Chen¹, Kang Chen², Liqun Wu¹, Zack Z. Wang²•Institutions (2)

Shanghai Jiao Tong University¹, Maine Medical Center²

01 May 2008-Journal of Cellular Biochemistry

TL;DR: This review will focus on extrinsic factors that play a role in regulating different stages of cardiomyocyte differentiation of ES cells in Pluripotent embryonic stem (ES) cells.

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Abstract: Cardiovascular disease is one of leading causes of death throughout the U.S. and the world. The damage of cardiomyocytes resulting from ischemic injury is irreversible and leads to the development of progressive heart failure, which is characterized by the loss of functional cardiomyocytes. Because cardiomyocytes are unable to regenerate in the adult heart, cell-based therapy of transplantation provides a potential alternative approach to replace damaged myocardial tissue and restore cardiac function. A major roadblock toward this goal is the lack of donor cells; therefore, it is urgent to identify the cardiovascular cells that are necessary for achieving cardiac muscle regeneration. Pluripotent embryonic stem (ES) cells have enormous potential as a source of therapeutic tissues, including cardiovascular cells; however, the regulatory elements mediating ES cell differentiation to cardiomyocytes are largely unknown. In this review, we will focus on extrinsic factors that play a role in regulating different stages of cardiomyocyte differentiation of ES cells.

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35 citations

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

...The FGFs and FGF receptors (FGFRs) have been implicated in a variety of physiological and pathological conditions, including mesodermal development, tissue growth and remodeling, inflammation, tumor growth, and vascularization [Xu et al., 1999; Powers et al., 2000]....
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Journal Article•DOI•

Defined feeder-free culture system of human embryonic stem cells

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Seon Hye Cheon, Sun Jong Kim, Jung Youn Jo, Won Jeong Ryu, Kunsoo Rhee, Sung Il Roh - Show less +2 more

19 Oct 2005-Biology of Reproduction

TL;DR: Three different Miz-hES cell lines were cultured for up to 7 months on human laminin in a novel, feeder layer-free cocktail medium containing growth factors and extracellular matrix molecules and showed normal telomere lengths, karyotypes and developmental potentials in vivo and in vitro.

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Abstract: 23 Most of human embryonic stem cells (hESCs) has been established and maintained on 24 a feeder layer and/or in mouse embryonic fibroblast (MEF)-conditioned media with animal25 origin supplements. These cells may be generally appropriate for basic research but not clinical 26 applications. In an effort to develop a feeder-free, xeno-free culture system for therapeutic 27 applications, we cultured three different Miz-hES cell lines for up to 7 months on human 28 laminin in a novel, feeder layer-free cocktail medium containing growth factors and 29 extracellular matrix molecules. All three of the cultured hESC lines retained appropriate 30 expression of transcription factors and surface antigens after prolonged culture, and showed 31 normal telomere lengths, karyotypes and developmental potentials in vivo and in vitro. These 32 findings indicate that our novel serumand feeder-free culture method may be useful for 33 generation at clinically applicable hESCs. 34 35

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35 citations

Journal Article•DOI•

Platelet-derived Growth Factor-BB and Basic Fibroblast Growth Factor Directly Interact in Vitro with High Affinity

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Katia Russo, Raffaele Ragone, Angelo Facchiano, Maurizio C. Capogrossi, Antonio Facchiano - Show less +1 more

11 Jan 2002-Journal of Biological Chemistry

TL;DR: The observed bFGF·PDGF-BB complex formation might explain, at least in part, previous observations showing that PDGF- BB chemotactic and mitogenic activity on smooth muscle cells are strongly inhibited in the presence of bF GF.

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35 citations

Patent•

Botulinum toxin screening assays

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Ester Fernandez-Salas¹, Patton E. Gary¹, Kei Roger Aoki¹•Institutions (1)

Allergan¹

23 Feb 2005

TL;DR: In this article, the authors present methods for detecting BoNT/A activity in a sample, methods for screening molecules able to compete with BoNT receptor binding and methods for reducing BoNT-A activity.

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Abstract: Methods for detecting BoNT/A activity in a sample, methods for screening molecules able to compete with BoNT/A receptor binding, methods for reducing BoNT/A activity in a human and methods of marketing a neurotoxin capable of selectively binding to FGFR3 to a governmental or regional regulatory authority.

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35 citations

Journal Article•DOI•

Recent Development in Applications of Important Biopolymer Chitosan in Biomedicine, Pharmaceuticals and Personal Care Products

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Gurpreet Singh Dhillon, Surinder Kaur, Saurabh Jyoti Sarma, Satinder Kaur Brar, Mausam P. Verma, Rao Y. Surampalli - Show less +2 more

28 Feb 2013

TL;DR: The biopolymer chitosan (CTS) has been gaining attention in the regenerative medicine due to its structural similarity to glycosaminoglycans, which are components of a tissue’s extracellular matrix.

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Abstract: In recent years, considerable attention has been given to functional biomaterials (BMs) for their potential applications in the biomedical field. Among them, the biopolymer chitosan (CTS) has been receiving increasing attention. Owing to its unique and appealing biological properties, such as biocompatibility, tunable biodegradability, antimicrobial, and wound healing activity, it is considered suitable for biomedical applications. CTS and its derivatives are promising candidates as a supporting material for tissue engineering applications due to their porous structure, gel forming properties, ease of chemical modification and high affinity to in vivo macromolecules. These BMs showed great potential due to their polyelectrolyte properties, the presence of reactive functional groups, high adsorption capacity, and anti-tumor effect. Remarkably, the application of CTS has been gaining attention in the regenerative medicine due to its structural similarity to glycosaminoglycans, which are components of a tissue’s extracellular matrix.

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35 citations

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

...Moreover, angiogenic growth factors, such as VEGF and FGF have been also reported to be linked with malignant tumors [105-106] and retinal neovascularization [107]....
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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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