Differential Regulation of Fibroblast Growth Factor (FGF) Receptor-1 mRNA and Protein by Two Molecular Forms of Basic FGF

Estival, A.; Monzat, Véronique; Miquel, Karine; Gaubert, F.; Hollande, E; Korc, Murray; Vaysse, Nicole; Clémente, F.

doi:10.1074/jbc.271.10.5663

Cited by 48 publications

(29 citation statements)

References 33 publications

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“…This suggests that, FGFR1 activation mediated by an autocrine/paracrine loop was the mechanism involved in reducing apoptosis in late passage cells because aged cells accumulated and secreted a higher amount of FGF1 and because inactivation of FGFR1 resulted in an increase in PCD. This is consistent with previous data showing that autocrine stimulation of growth factor receptors makes it possible for cells to resist PCD (39), whereas lower levels of FGFR1 signal transduction are involved in the inability of senescent endothelial cells to respond to exogenous FGF1 (40). mission of the FGF1 signal in RPE cells (28), JNK1 is implicated in the induction of apoptosis after growth factor deprivation (43), and ERK2 and JNK1 have opposing effects on cell death (44).…”

Section: Erk2 Activation and Synthesis In Aged Rpe Cellssupporting

confidence: 91%

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Guillonneau

Bryckaert²,

Launay-Longo³

et al. 1998

Journal of Biological Chemistry

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Retinal-pigmented epithelial (RPE) cell survival is critical to the maintenance of the function of the neural retinal and in the development of various retina degenerations. We investigated molecular mechanisms involved in this function by assessing apoptosis in RPE cells following serum deprivation. Apoptosis induced by serum withdrawal is lower in aged RPE cells because of higher endogenous acidic fibroblast growth factor (FGF1) synthesis and secretion. These experiments examined several aspects of FGF signaling and the contribution of endogenous FGF1 to activation of the extracellular signal-regulated kinase 2 (ERK2). In aged RPE cells, FGFR1 was rapidly activated, and its autophosphorylation followed the kinetics of endogenous FGF1 secretion, before the onset of apoptosis. ERK2 phosphorylation, activity, and de novo synthesis increased at the same time. In marked contrast, no de novo JNK1 synthesis was observed. MEK1 inhibition resulted in lower levels of ERK2 activation and synthesis and higher levels of apoptosis. Treatment with neutralizing anti-FGF1 or blocking anti-FGFR1 antibodies mimics these effects. Thus, this study strongly suggests that the survival-increasing effect of FGF1 in aged RPE cells is because of an autocrine/paracrine loop in which the ERK2 cascade plays a pivotal role. Fibroblast growth factors (FGFs)1 are a family of at least 15 polypeptides that stimulate growth and differentiation in cells of various mesenchymal and ectodermal origins. (for reviews, see Refs. 1-5). Acidic FGF (FGF1) and basic FGF (FGF2) are the prototype members of this family. FGF1 and 2 lack a classic signal peptide (6, 7), implying that they are not secreted by the classical secretion pathway. There is evidence that FGF1 and 2 are exported from the cell and subsequently act as autocrine or paracrine factors (8, 9). FGF1 and 2 exert their effects via high affinity tyrosine kinase receptors (FGFR1-FGFR4) (for reviews, see Refs. 10 -12) and via lower affinity heparan sulfate proteoglycan binding sites (13-15). FGFR activation causes tyrosine phosphorylation of the receptor itself, intracellular proteins including phospholipase C␥ (PLC␥) (16), extracellular signal-regulated kinases (ERKs) (17), and of several uncharacterized proteins of [80][81][82][83][84][85][86][87][88][89][90]19). All cell layers in normal adult retina produce FGF1, as cells no longer differentiate or proliferate. The pattern of FGF1 production suggests that FGF1 may be involved in the regulation of specific spatiotemporal events, including proliferation, migration, differentiation and survival in the retina. In vivo, despite the presence of FGFs in the retinal interphotoreceptor matrix, RPE cells have a limited proliferation capacity consistent with the normal increase in retinal space associated with growth and age. In adult, RPE cells cannot divide in vivo, but they may still require survival factors to inhibit their apoptosis. Cell survival and proliferation may be determined by the amount of factor available and the amount of receptor produc...

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Section: Erk2 Activation and Synthesis In Aged Rpe Cellssupporting

confidence: 91%

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Guillonneau

Bryckaert²,

Launay-Longo³

et al. 1998

Journal of Biological Chemistry

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“…The molecular basis for this downregulation could be indirect, such as through sequestration of endogenous bFGF. Previous studies showed upregulated cell surface expression of FGFR1 in pancreatic cell lines engineered to express low levels of the cytosolic 18 kDa, or nuclear targeted 22.5 kDa FGF2 isoforms, presumably by increasing the stability of FGFR1 gene transcript (Estival et al, 1996). It is thus possible that the reverse is also true, i.e.…”

Section: Discussionmentioning

confidence: 99%

Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases

Yayon

Safran

et al. 1997

Oncogene

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“…The different molecular weight forms of bFGF also show functional differences on FGF receptor function. It was reported that the 22.5-kDa isoform of the bFGF acts by increasing FGF receptor type 1 messenger RNA stability, thus enhancing cell responses to exogenous bFGF (73). It has been postulated that intracellular bFGF is released by alternative mechanisms (18).…”

Section: A B C D E F G Hmentioning

confidence: 99%

Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

Chadi

Fuxé

1998

Braz J Med Biol Res

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The actions of fibroblast growth factors (FGFs), particularly the basic form (bFGF), have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair.

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Differential Regulation of Fibroblast Growth Factor (FGF) Receptor-1 mRNA and Protein by Two Molecular Forms of Basic FGF

Cited by 48 publications

References 33 publications

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Endogenous FGF1-induced Activation and Synthesis of Extracellular Signal-regulated Kinase 2 Reduce Cell Apoptosis in Retinal-pigmented Epithelial Cells

Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases

Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

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