Requirement of Heparan Sulfate for bFGF-Mediated Fibroblast Growth and Myoblast Differentiation

Rapraeger, Alan C.; Krufka, Alison; Olwin, Bradley B.

doi:10.1126/science.1646484

Cited by 1,460 publications

(1,005 citation statements)

References 35 publications

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“…Additionally, FHFs and FGFs are similar in their affinity for heparin, which has aided in FHF protein purification (Olsen et al, 2003). While FGFs utilize extracellular heparan sulfate proteoglycan (HSPG) as an integral cofactor in receptor clustering (Rapraeger et al, 1991;Schlessinger et al, 2000;Yayon et al, 1991), FHFs reside in an intracellular environment lacking HSPGs. FHFs have conserved the heparin-binding domain for use in binding one of its protein targets (see below).…”

Section: Vertebrate Fhf Gene Expression and Protein Distributionmentioning

confidence: 99%

Fibroblast growth factor homologous factors: Evolution, structure, and function

Goldfarb¹

2005

Cytokine & Growth Factor Reviews

198

175

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SummaryFibroblast growth factor homologous factors (FHFs) bear strong sequence and structural similarity to fibroblast growth factors (FGFs). However, the biochemical and functional properties of FHFs are largely, if not totally, unrelated to those of FGFs. Whereas FGFs function through binding to the extracellular domains of FGF receptors (FGFRs), FHFs bind to intracellular domains of voltage-gated sodium channels (VGSCs) and to a neuronal MAP kinase scaffold protein, isletbrain-2 (IB2). These findings demonstrate the remarkable functional adaptability during evolution of the FGF gene family. FHF gene mutations in mice result in a range of neurological abnormalities, and at least one of these anomalies, cerebellar ataxia, is linked to FHF mutations in humans. This article reviews the sequences and structure of FHFs, along with our still limited understanding of FHF function.

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Section: Vertebrate Fhf Gene Expression and Protein Distributionmentioning

confidence: 99%

Fibroblast growth factor homologous factors: Evolution, structure, and function

Goldfarb¹

2005

Cytokine & Growth Factor Reviews

198

175

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“…The importance of cell-surface heparan sulphate in the activation of signalling receptors by growth factors was first suggested in studies which showed that a loss of cell-surface heparan sulphate, caused either by treatment with a metabolic inhibitor of heparan sulphate synthesis (sodium chlorate) [90] or mutation of a gene coding for an enzyme of heparan sulphate biosynthesis [91], resulted in the failure of bFGF to bind and activate the FGF-receptor kinase under the experimental conditions used. Many subsequent studies have confirmed these initial observations and have extended them to include other heparan sulphate-binding growth factors [84,85,88].…”

Section: Modulation Of Growth-factor-receptor Activationmentioning

confidence: 99%

Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

621

497

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This review will summarize our current state of knowledge of the structure, biochemical properties and functions of syndecans, a family of transmembrane heparan sulphate proteoglycans. Syndecans bind a variety of extracellular ligands via their covalently attached heparan sulphate chains. Syndecans have been proposed to play a role in a variety of cellular functions, including cell proliferation and cell–matrix and cell–cell adhesion. Syndecan expression is highly regulated and is cell-type- and developmental-stage-specific. The main function of syndecans appears to be to modulate the ligand-dependent activation of primary signalling receptors at the cell surface. Principal functions of the syndecan core proteins are to target the heparan sulphate chains to the appropriate plasma-membrane compartment and to interact with components of the actin-based cytoskeleton. Several functions of the syndecans, including syndecan oligomerization and actin cytoskeleton association, have been localized to specific structural domains of syndecan core proteins.

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“…TC-32 cells were grown in low serum conditions (0.5% FCS in RPMI 1640 media) for 24 h, and then treated with either aFGF (0.1, 1 or 10 ng ml À1 ) or bFGF (0.1, 1 or 10 ng ml À1 ) in low serum media containing heparin (10 U ml À1 ) for up to 30 min at 371C. Heparin was included in conditions for FGF treatment as its molecular association with FGF and its receptors is reported to be essential for biological activity (Rapraeger et al, 1991;Lin et al, 1999). Flasks were placed in ice, cells were washed in cold PBS and lysates were prepared in lysis buffer (50 mM HEPES (pH 7.5), 100 mM NaCl, 1 mM EGTA, 1 mM DTT, 10 mM MgCl 2 , 1% (v v À1 ) Triton X-100, 10 mg ml À1 aprotinin, 10 mg ml À1 leupeptin, 1 mM sodium orthovanadate (Sigma), 25 mM sodium fluoride (Sigma)).…”

Section: Activation Of Fgfr3 and Fgfr1 Following Exposure To Afgf Andmentioning

confidence: 99%

FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells

Merrick

2003

Br J Cancer

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Fibroblast growth factor receptor 3 (FGFR3) is one of four high-affinity tyrosine kinase receptors for the FGF family of ligands, frequently associated with growth arrest and induction of differentiation. The extracellular immunoglobulin (IgG)-like domains II and III are responsible for ligand binding; alternative usage of exons IIIb and IIIc of the Ig-like domain III determining the ligand-binding specificity of the receptor. By reverse transcriptase polymerase chain reaction (RT -PCR) a novel FGFR3IIIc variant FGFR3IIIS, expressed in a high proportion of tumours and tumour cell lines but rarely in normal tissues, has been identified. Unlike recently described nonsense transcripts of FGFR3, the coding region of FGFR3IIIS remains in-frame producing a novel protein. The protein product is coexpressed with FGFR3IIIc in the membrane and soluble cell fractions; expression in the soluble fraction is decreased after exposure to bFGF but not aFGF. Knockout of FGFR3IIIS using antisense has a growth-inhibitory effect in vitro, suggesting a dominantnegative function for FGFR3IIIS inhibiting FGFR3-induced growth arrest. In summary, alternative splicing of the FGFR3 Ig-domain III represents a mechanism for the generation of receptor diversity. FGFR3IIIS may regulate FGF and FGFR trafficking and function, possibly contributing to the development of a malignant phenotype.

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Requirement of Heparan Sulfate for bFGF-Mediated Fibroblast Growth and Myoblast Differentiation

Cited by 1,460 publications

References 35 publications

Fibroblast growth factor homologous factors: Evolution, structure, and function

Fibroblast growth factor homologous factors: Evolution, structure, and function

Syndecans: multifunctional cell-surface co-receptors

FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells

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