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Journal ArticleDOI

Fibroblast growth factors, their receptors and signaling.

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.
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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Citations
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Book ChapterDOI
01 Jan 2016
TL;DR: The novel topics in pulmonary fibrosis include the origin of lung fibroblasts, alveolar epithelial integrity, and resolution of extracellular matrixes and the mechanisms involved in the fibrogenesis in the lungs of IPF are clarified.
Abstract: The molecular pathogenesis in IPF is not fully understood. However, epithelial injury and subsequent aberrant wound healing, rather than chronic inflammation, are thought to play central roles in the recent hypothesis. Alveolar epithelial cells predisposed with genetic mutations may involve in the abnormal responses subsequent to injury. Growth factors, such as transforming growth factor-β and platelet-derived growth factors, are critical mediators that control the growth and differentiation of lung fibroblasts. The novel topics in pulmonary fibrosis include the origin of lung fibroblasts, alveolar epithelial integrity, and resolution of extracellular matrixes. The further studies are required to clarify the mechanisms involved in the fibrogenesis in the lungs of IPF.

2 citations

Dissertation
16 Jan 2019
TL;DR: Evidence that continuous age-related changes in the adipose vasculature modulate fat mass, adipocyte function, insulin sensitivity and blood lipid profiles is produced, and a therapeutic potential of FGF10 modulating miRNAs for treatment of obesity and related metabolic diseases is suggested.
Abstract: The adipose tissue is composed of a variety of cell types that constantly cross-communicate with each other to allow the tissue to operate and to adapt to various external stimuli. The diversity of these cell populations and their production of secretory factors define not only adipose tissue morphology, but also its function. This regulatory network is particularly important in times of adipose tissue remodeling and failure to adapt may result in severe malfunction of adipose tissues. Data presented in this thesis provide evidence that stromal vascular cells of the adipose tissue have important functions in adipose tissue remodeling and metabolic activation. We specifically focus on the role of various tyrosine kinase growth factor families such as VEGF, PDGF and FGF and their capacity to alter the adipose tissue microenvironment by their ability to remodel blood vessels or promote differentiation of vessel-associated cells into adipocytes. In paper I, we identified a miRNA-327-FGF10-FGFR2 autocrine regulatory loop that is fundamental for white adipocyte browning. We provide the first evidence that a miRNAdependent mechanism can control the differentiation of PDGFR-αP P cells into thermogenic beige cells. We further demonstrated that FGF10 is not only important for white adipocyte differentiation, but additionally possesses the ability to recruit and activate beige adipocytes. Finally, systemic inhibition of miRNA-327 induced white adipocyte browning, thereby improving whole-body metabolic rates and norepinephrine-induced thermogenesis in an FGF10 dependent manner. Our data suggest a therapeutic potential of FGF10 modulating miRNAs for treatment of obesity and related metabolic diseases. Paper II represents a detailed characterization of the function of VEGFR1 in the adipose tissue during browning and brown adipose tissue activation. Since VEGFR1 acts as a decoy receptor for VEGF, loss of VEGFR1 results in an increase of VEGF-VEGFR2 complex formation and thereby robust angiogenesis. The generation of two distinct endothelial cell specific knockout mouse strains allowed us to demonstrate that loss of VEGFR1 in endothelial cells is sufficient to induce adipose tissue angiogenesis and thereby white adipocyte browning and brown adipose tissue activation. Loss of VEGFR1 in adipocytes or myeloid cells, however, had no detectable effect on adipose tissues. Endothelial specific VEGFR1 KO mice were resistant to diet-induced obesity, resulting in improved insulin sensitivity and a reduction of ectopic lipid accumulation in the liver. Therefore, VEGFR1 blockade in endothelial cells represents an attractive approach to treat obesity, type 2 diabetes and liver steatosis. In paper III we demonstrate that angiogenic endothelial cells produce PDGF-CC, which results in white adipose tissue browning. We show that such white adipose tissue browning can be prevented by: 1) inhibition of angiogenesis by VEGFR2 blockade, 2) systemic knockout of Pdgfc, or 3) by treatment with a PDGFR-α neutralizing antibody; all resulted in the inability of WAT to undertake a beige phenotype. We could demonstrate that endothelial cells influence adipocyte function in a paracrine fashion by secreting PDGF-CC that drives PDGFR-αP P preadipocytes into beige adipocyte differentiation. Hence, we conclude that an increase in PDGF-CC levels or the activation of PDGFR-α downstream signaling in preadipocytes might be a novel treatment options for obese patients. In paper IV we asked the question why age is such a strong indicator for obesity and insulin resistance, and if blood vessels play a role. We produced evidence that continuous age-related changes in the adipose vasculature modulate fat mass, adipocyte function, insulin sensitivity and blood lipid profiles. In middle-aged mice, blood vessel numbers were low and VEGFR1 expression levels high, resulting in reduced vascular plasticity. Surprisingly, middle-aged mice on high-fat diet, but not standard chow, are highly sensitive to anti-VEGF treatment, which resulted in reduced body weight, improved HOMA-IR and enhanced glucose clearance. These findings indicate that low vascular plasticity in middle-aged individuals increases their risk to suffer from obesity and type-2 diabetes. Collectively, this thesis work uncovers important players in the cross talk between the adipose tissue vasculature and adipocytes, which lays the ground for the development of novel pharmaceutical approaches. POPULÄRVETENSKAPLIG SAMMANFATTNING Fettvävnader är viktiga i både lagring och användning av energi, och dessa vävnader består av olika typer av celler som kommunicerar med varandra. Sammansättningen av vävnaden, samt cellernas kommunikation spelar en avgörande roll för fettvävnadens korrekta funktion. Samspelet definierar bland annat om fettceller hellre lagrar eller bryter ner fett, och är speciellt viktig t.ex. under fastande, överdrivet kaloriintag, fysisk träning eller om kroppen är utsatt för extremt varma eller kalla temperaturer. Komplikationer som typ 2-diabetes eller kardiovaskulära sjukdomar kan förekomma under sådana förhållanden om fettvävnaden inte kan anpassa sig. Blodkärl levererar syre och näring till cellerna och är därför viktiga för kommunikation mellan celler i fettvävnaden och resten av kroppen. I vår forskning försöker vi förstå hur blodkärl kommunicerar med omgivningen i fettvävnader under speciella förhållanden, med avsikten att förändra blodkärlen för att förbättra eller förhindra fetma och diabetes. I den första publikationen identifierade vi en signal – så kallad FGF10 – som är särskilt viktig för kommunikation i fettvävnaden när kroppen utsätts för kalla temperaturer. Genom att öka den signalen lyckades vi öka förmågan av fettvävnader att producera värme när möss utsattes för kalla temperaturer (4 °C). Intressant nog kunde vi visa att den signalen kan leda till ett ökat antal värmeproducerande fettceller även vid rumstemperatur. Dessa resultat är viktiga eftersom värmeproduktion i fettvävnaden resulterar i ökat energibehov i hela kroppen och därför förbrukas fler kalorier hos möss med ökad mängd av den signalen. I 2:a publikationen analyserade vi en signalmottagare som finns på utsidan av cellerna och därigenom kan ta emot signaler från andra celler. Vi upptäckte att blockering eller borttagning av denna mottagare resulterade i fler antal blodkärl i fettvävnaden. Genom olika experiment såg vi hur ett ökat antal blodkärl ledde till: 1) mer värmeproducerande celler i fettvävnader vid exponering för kyla, och 2) ett motstånd mot viktökning i möss som matades med kaloririk mat. Dessa möss hade därmed minskad risk att utveckla diabetes eller fettlever. Vi drar slutsatsen att blockering av denna mottagare kan vara till nytta för patienter som lider av fetma, typ 2-diabetes eller fettleversjukdom. I 3:e publikationen visar vi att celler som utgör själva blodkärlen kan producera och skicka ut en signal som kan förändra fettcellernas funktion. Om antalet blodkärl minskas drastiskt eller denna signal avlägsnas kan fettceller inte längre producera värme när möss utsätts för kyla. Om istället signalen är högre än normalt kan vissa celler som tätt omger blodkärlen genomgå förändring till att bli fettceller och därigenom producera värme. I 4:e publikationen studerade vi blodkärlens roll i fettvävnaden i olika åldersgrupper och kunde hitta skillnader i antalet av blodkärl i fettvävnader och förmåga att anpassa sig till förändringar beroende på ålder. Möss i medelåldern hade färre blodkärl och en minskad förmåga att ändra antal av blodkärl. Foder med högt kaloriinnehåll gjorde däremot fettvävnaden av möss i medelåldern mera anpassningsbara. Intressant nog, så ökades möjligheten av blodkärl att anpassa sig i möss i medelåldern med fetma drastisk, vilket resulterade i lägre kroppsvikt och minskad risk för att utveckla diabetes efter blodkärlsförändrande medicinering. Dessa resultat tyder på att minskad förmåga av blodkärl att anpassa sig till förändringar hos individer i medelåldern ökar risken för fetma och diabetes. Sammanfattningsvis avslöjar denna avhandling viktiga delar i kommunikationen mellan blodkärl och fettceller, som i framtiden kan ligga till grund för utvecklingen av nya läkemedel för att behandla fetma och relaterade sjukdomar. POPULÄRWISSENSCHAFTLICHE ZUSAMMENFASSUNG Fettgewebe besteht aus einem Gemisch verschiedener Zellarten, die miteinander kommunizieren. Die Zusammensetzung dieser Zellen, sowie die Art und Weise, wie sie miteinander kommunizieren, ist wichtig für die korrekte Funktion des Fettgewebes. Diese Interaktion bestimmt unter anderem, ob Fettzellen Fett speichern oder abbauen und ist besonders wichtig während des Fastens, übermäßiger Kalorienzufuhr, intensiver körperlicher Aktivität und wenn der Körper extrem heißen oder kalten Temperaturen ausgesetzt ist. Wenn während dieser Situationen Probleme in der Kommunikation zwischen Zellen auftreten, kann das Fettgewebe Schwierigkeiten haben, sich anzupassen und Komplikationen wie Typ-2Diabetes oder Herz-Kreislauf-Erkrankungen können auftreten. Blutgefäße versorgen die Zellen mit Sauerstoff und Nährstoffen und sind daher besonders wichtig für die Kommunikation zwischen Zellen im Fettgewebe untereinander und mit dem Rest des Körpers. In unserer Forschung versuchen wir zu verstehen, wie Blutgefäße mit Fettzellen kommunizieren. Wir versuchen außerdem diese Kommunikation so zu beeinflussen, dass bereits bestehende Krankheiten im Fettgewebe behoben werden können. In der ersten Veröffentlichung identifizierten wir einen Kommunikationsfaktor, FGF10, der besonders wichtig für die Anpassung des Fettgewebes an kalte Temperaturen ist. Weiters fanden wir einen Weg, die Menge dieses Faktors zu erhöhen, was zu einer Steigerung der Wärmeproduktion im Fettgewebe führte. Nicht alle Fettzellen können Wärme produzieren und wir konnten zeigen, dass der identifizierte Kommunikationsfaktor sogar bei Raumtemperatur dazu führt, dass eine erhöhte Anzahl an wärmeprodu

2 citations

Dissertation
13 Sep 2007
TL;DR: These findings suggest that xHtrA1 may act as a positive feedback regulator of FGF signals that through proteolytic cleavage of proteoglycans allows long-range FGF signaling in the extracellular space.
Abstract: Fibroblast growth factors (FGFs) are important signaling molecules, whose activities need to be tightly controlled. We have recently identified the Xenopus homolog of HtrA1 (xHtrA1) in a direct screen for secreted proteins (Pera, Hou et al., 2005. Int. J. Dev. Biol. 49, 781-796). In this thesis, we show that xHtrA1 is co-expressed with FGF8 in the embryo, and that its expression is activated by FGF signals, suggesting that xHtrA1 belongs to the FGF8 synexpression group. Misexpression of xHtrA1 phenocopies multiple effects of FGFs, including posterior specification, mesoderm induction, neuronal differentiation, cell motility and proliferation. Downregulation of xHtrA1 activity via an antisense morpholino oligonucleotide or a polyclonal antibody leads to an overall phenotype reminiscent of FGF loss-of-function, with enlargement of head and reduction of ventroposterior structures. xHtrA1-MO also impairs mesoderm formation and neuronal differentiation. xHtrA1 cooperates with FGF! and requires intact FGF signaling pathway for its patterning activities. xHtrA1 stimulates FGF/ERK activity, induces the transcription of FGF4 and FGF8 and allows long-range FGF signaling. In biochemical experiments, we could demonstrate that Biglycan, Syndecan4 and Glypican4 are cleaved by xHtrA1. In microinjected Xenopus embryos, purified heparan sulfate and dermatan sulfate induce posteriorization, mesoderm induction and neuronal differentiation in an FGF-dependent manner. These findings suggest that xHtrA1 may act as a positive feedback regulator of FGF signals that through proteolytic cleavage of proteoglycans allows long-range FGF signaling in the extracellular space.

1 citations


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

  • ...FGFs participate in inflammation, repair and regeneration during wound healing (Powers et al., 2000), and dermatan sulfate is...

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  • ...9), as also observed upon activation of FGF signaling (Powers et al., 2000)....

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DissertationDOI
01 Jan 2010
TL;DR: In this article, the authors present a full-length Tissue Factor-Isoform and Apoptose in the kardiovaskularen system, which is used to detect the presence of cancer cells.
Abstract: 1\. Einleitung 1.1. Die Blutgerinnungskaskade 1.2. Tissue Factor 1.2.1. Die „full-length“ Tissue Factor-Isoform 1.2.2. Die losliche alternativ gespleiste Tissue Factor-Isoform 1.3. Die Signaltransduktionswege und Tissue Factor 1.4. Die Apoptose im Herzen 1.4.1. Die Apoptose im kardiovaskularen System 1.4.1. Tissue Factor und Apoptose 2\. Zielsetzung 3\. Material 3.1. Chemikalien und Substanzen 3.2. Kits 3.3. Puffer 3.4. Enzyme 3.5. Vektoren & siRNAs 3.6. Zellen 3.7. Tiere 3.8. Antikorper 3.9. Primer und Bedingungen fur die Polymerasekettenreaktion 3.10. Gerate 3.11 Sonstige Materialien 4\. Methoden 4.1 Versuchsaufbau 4.2 Zellkulturexperimente 4.2.1. Zellkultur mit HL-1 Zellen 4.2.2. Zellkultur mit primaren Zellen 4.2.3. Vitalitatstest und Kontaminationsanalyse 4.2.4. Die Stimulation von Zellen 4.3. Molekularbiologische Methoden 4.3.1. Extraktion und Quantifizierung von RNA 4.3.2. cDNA-Synthese 4.3.3. Polymerasekettenreaktion (PCR) 4.3.3.1. Semiquantitative PCR 4.3.3.2. Kolonie-PCR 4.3.4. Auftrennung von DNA- Amplifikaten mittels Gelelektrophorese 4.3.5. DNA-Extraktion aus dem Agarosegel 4.3.6. Klonierung von DNA-Fragmenten 4.3.6.1. Restriktion 4.3.6.2. Ligation 4.3.6.3. Transformation 4.3.6.4. Dauerkulturen 4.3.6.5. Plasmidisolation 4.3.7. Transfektion 4.3.8. TaqMan RealTime-PCR 4.3.9 Genotypisierung von Mausen/ Mauseembryos 4.4 Proteinbiochemische Methoden 4.4.1. Proteingewinnung aus Zellen 4.4.2. Proteinbestimmung 4.4.3. SDS- Polyacrylamid-Gelelektrophorese (SDS-PAGE) 4.4.4. Western- / Immun-Blot 4.5. Durchflusszytometrie 4.5.1. Fluoreszenzfarbung von Zellen/ Bestimmung der KI-67-Expression 4.5.2. CFSE-Proliferationsassay 4.5.3. Annexin-V-/ Propidiumiodit-Apoptoseassay 4.5.4. Transfektionseffizienz 4.6. Fluoreszenzfarbung und Fluoreszenzmikroskopie 4.7. Statistische Auswertung 5\. Ergebnisse 5.1. Die Uberexpression von murinem asTF in HL-1 Zellen sowie die Charakterisierung dieser Zellen 5.1.1. Die stabile Uberexpression von murinem asTF in HL-1 Zellen 5.1.2. Das Wachstumsverhalten der asTF-uberexprimierenden HL-1 Zellen 5.1.3. Das Apoptoseverhalten der asTF-uberexprimierenden HL-1 Zellen 5.2. Die Bedeutung von asTF fur die Signaltransduktion 5.2.1. Der Einfluss von asTF auf die Signaltransduktionswege Erk1/2 und PI3K/Akt 5.2.2. Die Expression von Bcl-2 Proteinen in HL-1 Zellen 5.2.3. Die Beteiligung von Bcl-xL an der asTF-vermittelten anti-apoptotischen Wirkung 5.3. Ex vivo - Versuche 5.3.1. Die Isolation von primaren murinen Kardiomyozyten und die Transfektion mit dem asTF-Expressionsplasmid 5.3.2. Das Apoptoseverhalten der asTF-uberexprimierenden primaren murinen Kardiomyozyten 5.3.3. Die Genexpression von Bcl-2 Proteinen und Akt in Abhangigkeit der asTF-Expression 5.3.4. Das Apoptoseverhalten von embryonalen Kardiomyozyten mit TF-Knockout 5.4. Der Einfluss von asTF auf die Expression von pro-angiogenen Proteinen 6\. Diskussion 6.1. Der Einfluss der asTF-Expression auf das Proliferationsverhalten und die Vitalitat der HL-1 Kardiomyozyten 6.2. Die Vermittlung der anti-apoptotischen Wirkung von asTF 6.3. Die Bedeutung von asTF fur das Uberleben primarer Kardiomyozyten 6.4. Die Bedeutung von asTF fur die Expression von Angiogenese-assoziierten Proteinen 6.5. Ausblick 7\. Zusammenfassung 8\. Summary 9\. Abkurzungsverzeichnis 10\. Literaturverzeichnis 11\. Publikationen 12\. Danksagung

1 citations

Dissertation
01 Jan 2006
TL;DR: In all systems studied, the stability of FGF-oligosaccharide-FR complexes correlated with the overall level of saccharide O-sulfation rather than on the precise distribution of sulfate groups.
Abstract: Biosynthesis of heparan sulfate (HS) is strictly regulated to yield products with cell/tissue-specific composition. Interactions between HS and a variety of proteins, including growth factors and morphogens, are essential for embryonic development and for homeostasis in the adult. Fibroblast growth factors (FGFs) and their various receptors (FRs) form ternary complexes with HS, as required for receptor signaling. Libraries of HS-related, radiolabeled oligosaccharides were generated by chemo-enzymatic modification of heparin and tested for affinity to immobilized FR ectodomains in the presence of FGF1 or FGF2. Experiments were designed to enable assessment of N-sulfated 8- and 10-mers with defined numbers of iduronic acid 2-O-sulfate and glucosamine 6-O-sulfate groups. FGF1 and FGF2 were found to require similar oligosaccharides in complex formation with FR1c-3c, FGF2 affording somewhat more efficient oligosaccharide recruitment than FGF1. FR4, contrary to FR1c-3c, bound oligosaccharides at physiological ionic conditions even in the absence of FGFs, and this interaction was further promoted by FGF1 but not by FGF2. In all systems studied, the stability of FGF-oligosaccharide-FR complexes correlated with the overall level of saccharide O-sulfation rather than on the precise distribution of sulfate groups.

1 citations


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

  • ...Alternative splicing and expression of different FR genes gives rise to a variety of FRs on different cells (Powers et al., 2000)....

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  • ...Some FGFs are expressed through several stages of the embryonic development, whereas others are expressed localized during specific timepoints (Powers et al., 2000; Ford-Perriss et al., 2001)....

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  • ...FGFs, being a large family 21 of proteins, are involved in a wide array of biological processes (reviewed in (Powers et al., 2000))....

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  • ...21 of proteins, are involved in a wide array of biological processes (reviewed in (Powers et al., 2000))....

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References
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Journal ArticleDOI
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.

2,448 citations

Journal ArticleDOI
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.
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.

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 ArticleDOI
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.
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.

2,364 citations

Journal ArticleDOI
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.

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 ArticleDOI

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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