Fibroblast growth factors, their receptors and signaling.

doi:10.1677/ERC.0.0070165

Home
/
Papers
/
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.

read less

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.

...read moreread less

Content maybe subject to copyright Report

Citations

PDF

Open Access

More filters

Dissertation•

Characterization of the expression and function of the early response 1 gene in Xenopus laevis embryonic development

[...]

Hema Artee Luchman

01 Jan 2002

TL;DR: The results suggest that ER1 may function as an endogenous, negative regulator of the FGF signaling pathway during Xenopus embryogenesis, and downregulates the expression of Xbra, BMP-4, and HoxB9.

...read moreread less

Abstract: Xenopus early response gene 1 is a maternally-derived immediate-early gene whose expression is activated by FGF during mesoderm induction in Xenopus embryos. The purpose of this project was to characterize the expression and investigate the function of ER1 protein during early development in Xenopus. Analysis of the expression pattern of ER1 showed that the protein is present in the early embryo but retained in the cytoplasm until mid-blastula stages after which it is translocated to the nucleus, first in the presumptive mesoderm, then in the presumptive ectoderm, and finally in the endoderm. Overexpression of the dominant negative FGF receptor XFD completely blocks translocation of ER1 to the nucleus at mid-blastula suggesting that nuclear translocation of ER1 is dependent on events triggered by FGF signaling. Deletion analysis of stretches of acidic amino acid in the N-terminal region of ER1 showed that the protein has transactivation activity in vitro, suggesting that the protein may function as a transcription factor in vivo. Overexpression of ER1 in embryos results in embryos with posterior truncations, a phenotype similar to that of embryos overexpressing XFD. RT-PCR analysis of molecular markers expressed during early development showed that overexpression of ER1 downregulates the expression of Xbra, BMP-4, and HoxB9. These results suggest that ER1 may function as an endogenous, negative regulator of the FGF signaling pathway during Xenopus embryogenesis.

...read moreread less

3 citations

The Mechanisms Underlying Cocaine-Induced Overexpression of Basic Fibroblast Growth Factor (bFGF, FGF2), an Effect Reversed By Extinction

[...]

Madalyn Hafenbreidel

01 Jan 2016

TL;DR: Extinction of drug seeking can reduce bFGF expression in IL-mPFC, nucleus accumbens (NAc), and dorsal hippocampus (dHipp), indicating that bF GF may mediate drug-associated learning, however, the circuitry and mechanisms underlying extinction and the role ofbFGF is unknown.

...read moreread less

Abstract: THE MECHANISMS UNDERLYING COCAINE-INDUCED OVEREXPRESSION OF BASIC FIBROBLAST GROWTH FACTOR (BFGF, FGF2), AN EFFECT REVERSED BY EXTINCTION by Madalyn Hafenbreidel The University of Wisconsin-Milwaukee, 2016 Under the Supervision of Devin Mueller Drug addiction is characterized by compulsive drug use and chronic relapse despite negative consequences. Drug-induced structural and functional changes in the brain are thought to underlie these characteristics. One mechanism that may mediate these characteristics are growth factors, such as basic fibroblast growth factor (bFGF or FGF2), as they are necessary for cellular growth, survival, differentiation, and have roles in memory, mood, and anxiety disorders. bFGF mRNA and protein expression is increased following stimulant administration and is necessary for stimulant-induced changes in dendrites and behavioral sensitization. Moreover, addiction is maintained by cues associated with the drug, as they can can evoke craving and promote relapse. Therefore, reducing cue reactivity, such as with extinction, could reduce relapse rates. Inhibiting bFGF in the infralimbic medial prefrontal cortex (IL-mPFC), following selfadministration, facilitates extinction. Extinction of drug seeking can reduce bFGF expression in IL-mPFC, nucleus accumbens (NAc), and dorsal hippocampus (dHipp), indicating that bFGF may mediate drug-associated learning. However, the circuitry and mechanisms underlying extinction and the role of bFGF is unknown. Therefore, the

...read moreread less

3 citations

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

...bFGF is part of a large and functionally diverse fibroblast growth factor family, which is composed of 23 different FGF types and subfamilies (FGF1-23), ten of which are localized to the brain (Burgess & Maciag, 1989; Powers et al., 2000; Reuss & von Bohlen und Halbach, 2003)....
[...]
...bFGF is expressed in both neurons and glia, but preferentially in glia (Eckenstein, Woodward, & Nishi, 1991; Gomez-Pinilla, Lee, & Cotman, 1994; Gonzalez, Berry, Maher, Logan, & Baird, 1995; Reuss & von Bohlen und Halbach, 2003), and a higher molecular weight form of bFGF is specifically expressed in the nucleus, though its function is currently unclear (Arnaud et al., 1999; Bugler, Amalric, & Prats, 1991; Coulier et al., 1997; Powers et al., 2000)....
[...]
...Ras belongs to a superfamily that mediates a number of downstream proteins and pathways, including the Raf/MEK (mitogen-activated protein kinase kinase)/ERK/MAPK (mitogen/extracellular-signal regulated kinase) pathway, which can activate a number of transcription factors, including CREB (cAMP response element binding; Graham & Richardson, 2011b; Lu, Koya, Zhai, Hope, & Shaham, 2006; Nestler, 2013; Powers et al., 2000; Zubilewicz et al., 2001)....
[...]
...…growth factor family, which is composed of 23 different FGF types and subfamilies (FGF1-23), ten of which are localized to the brain (Burgess & Maciag, 1989; Powers et al., 2000; Reuss & von Bohlen und Halbach, 2003). bFGF has a broad range of functions throughout development and adulthood....
[...]
...…Berry, Maher, Logan, & Baird, 1995; Reuss & von Bohlen und Halbach, 2003), and a higher molecular weight form of bFGF is specifically expressed in the nucleus, though its function is currently unclear (Arnaud et al., 1999; Bugler, Amalric, & Prats, 1991; Coulier et al., 1997; Powers et al., 2000)....
[...]

Book Chapter•DOI•

Growth factors and guided bone regeneration

[...]

Fawad Javed¹, Zohaib Akram², Junad Khan¹, Muhammad Sohail Zafar³, Muhammad Sohail Zafar⁴ - Show less +1 more•Institutions (4)

University of Rochester¹, Ziauddin University², Taibah University³, Riphah International University⁴

01 Jan 2020

TL;DR: This chapter has described the current knowledge concerning different types of GF and their role in the homeostasis of bone functions and healing.

...read moreread less

Abstract: The process of bone formation and remodeling is controlled by systemic regulation through various hormones such as calcitonin, parathormone, and growth factors (GF). It has been suggested that regional bone GF are expressed in the autocrine or paracrine fashion on bone cells influencing cellular and molecular mechanisms. These regulatory mechanisms are critical in preserving continuous amount of bone in the course of physiologic and diseased conditions (osteoporosis), or fracture healing. GF may contribute to augment implant abutment healing, regeneration, and repair of bone. This chapter has described the current knowledge concerning different types of GF and their role in the homeostasis of bone functions and healing.

...read moreread less

3 citations

Patent•

Compounds capable of affecting differentiation, proliferation, regeneration, plasticity and survival of cells

[...]

Vladislav V. Kiselyov, Galina Skladchikova, Vladimir Berezin, Elisabeth Bock

19 Aug 2002

TL;DR: In this article, a compound comprising the third Immunoglobulin (Ig3) module, and/or the fourth Immunoglobalin(Ig4) module; the fifth immunoglobulins (i.e., Ig5) module and the first Fibronectin III (Fn3, 1) module of neural cell adhesion molecule (NCAM), or a fragment, or a variant thereof, is described.

...read moreread less

Abstract: The present invention relates to a compound comprising the third Immunoglobulin (Ig3) module, and/or the fourth Immunoglobulin (Ig4) module, and/or the fifth Immunoglobulin (Ig5) module, and/or the first Fibronectin III (Fn3, 1) module, and/or the second Fibronectin III (Fn3, 2) module of neural cell adhesion molecule (NCAM), or a fragment, or a variant thereof, capable of interacting with a Fibroblast Growth Factor (FGF) receptor and/or Adenosine-Tri-Phosphate (ATP) and/or L1, and thereby the compounds are capable of inducing differentiation, modulating proliferation, stimulate regeneration, neuronal plasticity and/or survival of cells. Further, the present invention relates to a pharmaceutical composition comprising said compound, a process of producing a pharmaceutical composition and the use of said compound.

...read moreread less

3 citations

Dissertation•

Molecular pharmacodynamics of chemotherapy: fibroblast growth factor (FGF) inhibitors as chemosensitizers

[...]

Colin Walsh¹•Institutions (1)

Ohio State University¹

01 Jan 2005

3 citations

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

...It should be noted that FGFR2 IIIb is a high affinity receptor for aFGF but not bFGF (see Table 1 in [70])....
[...]

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

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

[...]

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.

...read moreread less

2,448 citations

Journal Article•DOI•

Protein modules and signalling networks

[...]

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.

...read moreread less

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.

...read moreread less

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)....
[...]
...Phosphorylated tyrosine residues, in turn, recruit other signaling molecules to the activated receptors and propagate the signal through many possible transduction pathways (Pawson 1995)....
[...]

Journal Article•DOI•

Thalidomide is an inhibitor of angiogenesis.

[...]

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.

...read moreread less

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.

...read moreread less

2,364 citations

Journal Article•DOI•

Receptor specificity of the fibroblast growth factor family.

[...]

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.

...read moreread less

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…...
[...]
...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…...
[...]
...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)....
[...]
...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)....
[...]

Journal Article•DOI•

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

[...]

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....
[...]