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

Journal Article•DOI•

Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity

[...]

David Kuninger¹, Alistair Wright², Alistair Wright¹, Peter Rotwein•Institutions (2)

Oregon Health & Science University¹, Dalhousie University²

03 May 2006-American Journal of Physiology-cell Physiology

TL;DR: A role is defined for p300 in promoting cell survival, which is independent of its acetyltransferase activity and acts at least in part through FGF-1.

...read moreread less

Abstract: Normal skeletal muscle development requires the proper orchestration of genetic programs by myogenic regulatory factors (MRFs). The actions of the MRF protein MyoD are enhanced by the transcription...

...read moreread less

11 citations

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

...Binding of FGFs to FGFRs rapidly leads to receptor dimerization and tyrosine autophosphorylation....
[...]
...Receptor dimerization appears to be mediated by a complex of heparin sulfate proteoglycans containing several FGFs (38)....
[...]
...Heparin sulfate proteoglycans also serve as a storage pool for FGFs and, along with other FGF binding proteins, additionally modulate biological effects by sequestration, enhancement of local growth factor concentrations in the extracellular matrix, or regulation of access to cell-surface FGFRs....
[...]
...The family now contains at least 22 members, whose actions are mediated by transmembrane receptors and extracellular heparin sulfate proteoglycans (38)....
[...]
...Ligand binding leads to receptor tyrosine phosphorylation and activation of several signal transduction pathways, including the Ras-RafMek-ERK cascade (22, 38)....
[...]

Journal Article•DOI•

Synthetic NCAM-derived Ligands of the Fibroblast Growth Factor Receptor

[...]

Stine Maria Hansen¹, Shizhong Li¹, Elisabeth Bock¹, Vladimir Berezin¹•Institutions (1)

University of Copenhagen¹

22 Apr 2008-Neurochemical Research

TL;DR: Four peptide sequences, FGL, BCL, dekaCAM, and FRM, encompassing various FN3 module loop regions, have been identified as FGFR ligands, which activate FGFR and differentially modulate a number of neuronal functions, such as differentiation, survival, and synaptic changes that are important for learning, memory, and neuronal regeneration.

...read moreread less

Abstract: The neural cell adhesion molecule (NCAM) responds to cues in the external environment and transmits signals to the cell through extracellular and intracellular interactions with a number of other signal transduction molecules. One such NCAM interaction partner is the fibroblast growth factor receptor (FGFR). NCAM interacts with FGFR via two fibronectin type III (FN3) modules in the extracellular part of NCAM. These modules consist of β-strands and connecting loop regions. On the basis of the structural analysis of the NCAM FN3 modules, four peptide sequences, FGL, BCL, dekaCAM, and FRM, encompassing various FN3 module loop regions, have been identified as FGFR ligands. All four peptides activate FGFR and differentially modulate a number of neuronal functions, such as differentiation, survival, and synaptic changes that are important for learning, memory, and neuronal regeneration.

...read moreread less

11 citations

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

...Four major transmembrane isoforms of FGFR tyrosine kinases have been identified in the brain (termed FGFR1-4) that have a prototypic extracellular domain structure consisting of three Ig domains (Ig1-3) with a long linker region between Ig1 and Ig2 [36]....
[...]

Journal Article•DOI•

Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls

[...]

Fu-Ying Tian¹, Xi-Meng Wang¹, Chuanbo Xie¹, Bo Zhao², Zhongzheng Niu³, Lijun Fan¹, Marie-France Hivert, Wei-Qing Chen¹ - Show less +4 more•Institutions (3)

Sun Yat-sen University¹, Boston Children's Hospital², University at Buffalo³

22 Mar 2018-Clinical Epigenetics

TL;DR: It is suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner and supported the importance of placental epigenetic changes in placental development and fetal growth.

...read moreread less

Abstract: Fibroblast growth factor receptor 2 (FGFR2) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association. We conducted analyses for each of the five valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and found that per one standard deviation increase in the DNA methylation of CpG 11 at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in placental surface area (β = − 0.18; standard error = 0.08, p = 0.02). The mediation effect of placental surface area on the association between DNA methylation and full-term low birth weight was significant in girls (OR = 1.38, 95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was 48.38%. Our findings suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner. Our study supported the importance of placental epigenetic changes in placental development and fetal growth.

...read moreread less

11 citations

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

...Fibroblast growth factors (FGFs) are critical in the regulation of implantation process of the placenta, including trophoblast differentiation, hormone production [21], and migration [22]....
[...]

Journal Article•DOI•

Herbimycin A inhibits angiogenic activity in endothelial cells and reduces neovascularization in a rat model of retinopathy of prematurity.

[...]

Gary W. McCollum¹, V.S. Rajaratnam¹, Lawrence E. Bullard¹, Rong Yang¹, John S. Penn¹ - Show less +1 more•Institutions (1)

Vanderbilt University¹

01 May 2004-Experimental Eye Research

TL;DR: Based on the results of this study, herbimycin A inhibits endothelial cell proliferation and tube formation at non-toxic concentrations and reduces pre-retinal neovascularization in a rat model of retinopathy of prematurity.

...read moreread less

11 citations

Journal Article•DOI•

Homozygous Mutation of the FGFR1 Gene Associated with Congenital Heart Disease and 46,XY Disorder of Sex Development

[...]

Inas Mazen, Heba Amin, Alaa K. Kamel, Mona O El Ruby, Joelle Bignon-Topalovic, Anu Bashamboo, Ken McElreavey - Show less +3 more

08 Apr 2016-Sexual Development

TL;DR: Exome sequencing revealed novel homozygous mutations in the FGFR1 and STARD3 genes that may be associated with the phenotype of a 46,XY patient with CHD associated with ambiguous genitalia consisting of a clitoris-like phallus and a bifid scrotum.

...read moreread less

Abstract: Congenital heart diseases (CHDs) are the most common cause of all birth defects and account for nearly 25% of all major congenital anomalies leading to mortality in the first year of life. Extracardiac anomalies including urogenital aberrations are present in ∼30% of all cases. Here, we present a rare case of a 46,XY patient with CHD associated with ambiguous genitalia consisting of a clitoris-like phallus and a bifid scrotum. Exome sequencing revealed novel homozygous mutations in the FGFR1 and STARD3 genes that may be associated with the phenotype.

...read moreread less

11 citations

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

...FGFR1 is tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and is essential in the regulation of embryonic development, cell proliferation, differentiation, and migration [Powers et al., 2000; Presta et al., 2005; Chen and Forough, 2006]....
[...]

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
…
166
167
168
169
170
171
172
…
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200

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....
[...]