Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1

Vainikka, Satu; Joukov, Vladimir; Wennström, Stefan; Bergman, M; Pelicci, P. G.; Alitalo, Kari

doi:10.1016/s0021-9258(17)32309-8

Cited by 127 publications

(23 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is therefore possible that myoblasts lacking FGFR4 may be regulated differently by FGFs than myoblasts expressing FGFR4. This suggestion is supported by studies of rat L6 myoblasts that were transfected with FGFR1 and FGFR4 (Vainikka et al 1994;Wang et al 1994;Shaoul et al 1995). The FGFR1-expressing cells showed a far more robust activation of the ERK1/ ERK2 mitogen-activated protein kinase signaling cascade compared to the FGFR4-expressing cells.…”

Section: Unique Expression and Possible Role Of Fgfr4 During Myogenesis Of Satellite Cellsmentioning

confidence: 82%

Gene Expression Patterns of the Fibroblast Growth Factors and Their Receptors During Myogenesis of Rat Satellite Cells

Kästner

Elias

Rivera

et al. 2000

J Histochem Cytochem.

183

193

View full text Add to dashboard Cite

S U M M A R Y Satellite cells are the myogenic precursors in postnatal muscle and are situated beneath the myofiber basement membrane. We previously showed that fibroblast growth factor 2 (FGF2, basic FGF) stimulates a greater number of satellite cells to enter the cell cycle but does not modify the overall schedule of a short proliferative phase and a rapid transition to the differentiated state as the satellite cells undergo myogenesis in isolated myofibers. In this study we investigated whether other members of the FGF family can maintain the proliferative state of the satellite cells in rat myofiber cultures. We show that FGF1, FGF4, and FGF6 (as well as hepatocyte growth factor, HGF) enhance satellite cell proliferation to a similar degree as that seen with FGF2, whereas FGF5 and FGF7 are ineffective. None of the growth factors prolongs the proliferative phase or delays the transition of the satellite cells to the differentiating, myogenin ϩ state. However, FGF6 retards the rapid exit of the cells from the myogenin ϩ state that routinely occurs in myofiber cultures. To determine which of the above growth factors might be involved in regulating satellite cells in vivo, we examined their mRNA expression patterns in cultured rat myofibers using RT-PCR. The expression of all growth factors, excluding FGF4, was confirmed. Only FGF6 was expressed at a higher level in the isolated myofibers and not in the connective tissue cells surrounding the myofibers or in satellite cells dissociated away from the muscle. By Western blot analysis, we also demonstrated the presence of FGF6 protein in the skeletal musle tissue. Our studies therefore suggest that the myofibers serve as the main source for the muscle FGF6 in vivo. We also used RT-PCR to analyze the expression patterns of the four tyrosine kinase FGF receptors (FGFR1-FGFR4) and of the HGF receptor (c-met) in the myofiber cultures. Depending on the time in culture, expression of all receptors was detected, with FGFR2 and FGFR3 expressed only at a low level. Only FGFR4 was expressed at a higher level in the myofibers but not the connective tissue cell cultures. FGFR4 was also expressed at a higher level in satellite cells compared to the nonmyogenic cells when the two cell populations were released from the muscle tissue and fractionated by Percoll density centrifugation. The unique localization patterns of FGF6 and FGFR4 may reflect specific roles for these members of the FGF signaling complex during myogenesis in adult skeletal muscle. Satellite cells are the myogenic precursors in postnatal and adult muscle. At least some of the satellite cells are mitotically active in the growing muscle, contributing myonuclei to the enlarging fibers. As muscle matures, the addition of myofiber nuclei ceases and the satellite cells become mitotically quiescent. Recruitment of these quiescent precursors occurs in response to overt muscle injury and to more subtle stresses such as stretch, exercise, and muscle hypertrophy. Depending on the degree of injury, the satellite cell prog...

show abstract

Section: Unique Expression and Possible Role Of Fgfr4 During Myogenesis Of Satellite Cellsmentioning

confidence: 82%

Gene Expression Patterns of the Fibroblast Growth Factors and Their Receptors During Myogenesis of Rat Satellite Cells

Kästner

Elias

Rivera

et al. 2000

J Histochem Cytochem.

183

193

View full text Add to dashboard Cite

show abstract

“…Second, there are a large of SV40 large T antigen, which is recognized by the mAb KT3 (MacArnumber of FGFRs (by virtue of the fact that there are thur and Walter, 1984). The epitope tag, stop codon, and restriction four genes and many splice variants), and they do not sites to aid subcloning were created by annealing and ligating the following oligodeoxynecleotides to Msc 1-digested FGFR1: all signal in an identical manner (Vainikka et al, 1994).…”

Section: Activation and Might Involve Direct Effects Of Fgf In Thementioning

confidence: 99%

Expression of a Dominant Negative FGF Receptor Inhibits Axonal Growth and FGF Receptor Phosphorylation Stimulated by CAMs

Saffell

Williams

Mason

et al. 1997

Neuron

316

243

View full text Add to dashboard Cite

The cell adhesion molecules (CAMs) NCAM, N-cadherin, and L1 are homophilic binding molecules that stimulate axonal growth. We have postulated that the above CAMs can stimulate this response by activating the fibroblast growth factor receptor (FGFR) in neurons. In the present study, we demonstrate that activation of NCAM and L1 can lead to phosphorylation of the FGFR. Both this and the neurite outgrowth response stimulated by all three of the above CAMs are lost when a kinase-deleted, dominant negative form of FGFR1 is expressed in PC12 cells. In addition, we have generated transgenic mice that express the dominant negative FGFR under control of the neuron-specific enolase (NSE) promoter. We show that cerebellar neurons isolated from these mice have also lost their ability to respond to NCAM, N-cadherin, and L1. A peptide inhibitor of phospholipase C gamma (PLCgamma) that inhibits neurite outgrowth stimulated by FGF also inhibited neurite outgrowth stimulated by the CAMs. Thus, we conclude that activation of the FGFR is both necessary and sufficient to account for the ability of the above CAMs to stimulate axonal growth, and that PLCgamma is a key downstream effector of this response.

show abstract

“…Although they showed encouraging progress, there remains an urgent need to develop new therapies for HCC. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that selectively binds fibroblast growth factor 19 (FGF19) to activate a series of reactions, leading to bile formation, cell differentiation and cell proliferation (Vainikka et al, 1994;Wu et al, 2011). Aberrant FGF19-FGFR4 complex formation has been identified as oncogenic in up to 32% of patients with HCC (Guichard et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

P-glycoprotein (ABCB1/MDR1) limits brain accumulation and Cytochrome P450-3A (CYP3A) restricts oral availability of the novel FGFR4 inhibitor fisogatinib (BLU-554)

Sparidans

El-Lari

et al. 2020

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1

Cited by 127 publications

References 60 publications

Gene Expression Patterns of the Fibroblast Growth Factors and Their Receptors During Myogenesis of Rat Satellite Cells

Gene Expression Patterns of the Fibroblast Growth Factors and Their Receptors During Myogenesis of Rat Satellite Cells

Expression of a Dominant Negative FGF Receptor Inhibits Axonal Growth and FGF Receptor Phosphorylation Stimulated by CAMs

P-glycoprotein (ABCB1/MDR1) limits brain accumulation and Cytochrome P450-3A (CYP3A) restricts oral availability of the novel FGFR4 inhibitor fisogatinib (BLU-554)

Contact Info

Product

Resources

About