Cell density regulates the number of cell surface receptors for fibroblast growth factor

Veomett, George E.; Kuszynski, Charles; Kazakoff, Peter; Rizzino, Angie

doi:10.1016/0006-291x(89)90050-8

Cited by 42 publications

(13 citation statements)

References 9 publications

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“…These findings are in accordance with previous reports using fetal pulmonary artery endothelial cells [26]. Cell density can also regulate the function and expression of growth factor receptors like FGFR1 [27]. Thus, the responses to each growth factor may vary according to cell density.…”

Section: Discussionsupporting

confidence: 93%

“…In oFPAE cells, cells that were sparser were more sensitive to FGF2 induction of eNOS expression while confluent cells did not respond. These results may arise, in part, from reduced membranebound FGF receptors with increasing cell density, which in turn leads to decreased binding of FGFs to their receptors on a per cell basis [27], a hypothesis that awaits further confirmation in our cell system.…”

Section: Discussionmentioning

confidence: 87%

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Differential Activation of Multiple Signalling Pathways Dictates eNOS Upregulation by FGF2 but not VEGF in Placental Artery Endothelial Cells

et al. 2008

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Fibroblast growth factor (FGF2), but not vascular endothelial growth factor (VEGF), upregulates endothelial nitric oxide synthase (eNOS) protein expression, at least in part, via activation of extracellular signal-regulated kinase 2/1 (ERK2/1) in ovine fetoplacental artery endothelial (oFPAE) cells. Herein we further investigated the temporal effects of FGF2 and VEGF on other signaling pathways including members (Jun N-terminal kinase JNK1/2 and p38MAPK) of mitogen-activated protein kinases (MAPK), phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene homolog 1 (PI3K/AKT1), and the tyrosine kinase c-SRC, and examined if either one or more of these pathways play a role in the differential regulation of eNOS by FGF2 and VEGF. We first confirmed that in oFPAE cells, FGF2, but not VEGF, increased eNOS protein. FGF2 stimulated eNOS protein in a time and concentration dependent manner, which also depended on cell density. FGF2 provoked sustained (5 min to 12 h) whereas VEGF only stimulated transient (5 min) ERK2/1 phosphorylation. FGF2 was 1.7-fold more potent in stimulating ERK2/1 phosphorylation than VEGF. FGF2 and VEGF only transiently activated JNK1/2 and AKT1 within 5 min; however, FGF2 was a stronger stimulus than VEGF. FGF2 and VEGF did not significantly activate p38MAPK at 5 min; however, VEGF stimulated p38MAPK phosphorylation at 60 min. VEGF but not FGF2 significantly stimulated c-SRC phosphorylation. Inhibitors of MEK-ERK2/1 (PD98059), JNK1/2 (SP600125) and PI3K (wortmannin), but not p38MAPK (SB203580) and SRC (PP2), decreased the FGF2-increased eNOS protein expression. Thus, the FGF2-induced eNOS protein expression requires activation of multiple signaling pathways including ERK2/1, JNK1/2 and PI3K/AKT1. Differences in intensity and temporal patterns of activation of these pathways by FGF2 and VEGF may account for their differential effects on eNOS expression in OFPAE cells.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 87%

Differential Activation of Multiple Signalling Pathways Dictates eNOS Upregulation by FGF2 but not VEGF in Placental Artery Endothelial Cells

et al. 2008

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“…Since all the endothelial cells are likely to be exposed to the same concentration ofcirculating bFGF, other factors must be modulating the process. One possibility is that the number of bFGF receptors varies between these two cell populations and number is high when cell density is low (24), and the endothelial cells at the leading edge would be considered a zone of low density. Ifthis was true then the lack ofavailability ofbFGF to the endothelium would be a dominant fact explaining why these cells stop replicating soon after denudation.…”

Section: Discussionmentioning

confidence: 99%

Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries.

Lindner¹,

Majack²,

Reidy³

1990

J. Clin. Invest.

270

114

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A large percentage of vascular reconstructions, endarterectomies, and angioplasties fail postoperatively due to thrombosis and restenosis. Many of these failures are thought to result from an inability of the vascular endothelium to adequately regenerate and cover the denuded area. After balloon catheter denudation of the rat carotid artery, regrowth of endothelium ceases after -6 wk, leaving a large area devoid of endothelium. Here we show that this cessation of reendothelialization can be overcome by the systemic administration of basic fibroblast growth factor (bFGF). Administration of 120 tig bFGF over an 8-h period caused a highly significant increase in the replication rate of endothelial cells at the leading edge of 38.5 vs. 2.1% in controls, and, when given over a longer period of time (12 ,g daily for 12 d), resulted in a significant increase in the extent of endothelial outgrowth onto the denuded surface. Furthermore, total regrowth could be achieved within 10 wk after balloon catheter denudation when 12 Mig bFGF was injected twice per week for a period of 8 wk. Endothelium in unmanipulated arteries responded to bFGF with a significant increase in replication, but no increase in endothelial cell density was observed in these arteries. These data demonstrate that bFGF can act as a potent mitogen for vascular endothelial cells in vivo, and add considerably to our understanding of the mechanism underlying endothelial repair after in vivo vascular

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“…Low-affinity binding sites have also been described and appear to be glycosaminoglycans (14,15). High-affinity FGF receptors are lost permanently during mouse skeletal muscle-cell terminal differentiation in vitro (16) and are reduced at high cell density (17). Further investigation of these phenomena would be greatly facilitated with molecular probes for studies of FGF receptor expression.…”

mentioning

confidence: 99%

Receptor for acidic fibroblast growth factor is related to the tyrosine kinase encoded by the fms-like gene (FLG).

Ruta¹,

Burgess²,

Givol³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

172

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We have previously isolated a human gene from an endothelial cell cDNA library encoding a putative tyrosine kinase; we have designated this gene thefms-like gene (FLG). To analyze the gene product(s) of FLG, we have generated rabbit polyclonal antibodies directed against a synthetic peptide from FLG and used it to immunoprecipitate biosynthetically labeled FLG protein from a variety of human cell lines. These antibodies specifically recognized glycoprotein(s) of 100, 120, and 135 kDa with protein cores of 90 and 110 kDa. Acidic fibroblast growth factor (aFGF) stimulated tyrosine kinase activity of FLG in vitro and in living cells, suggesting that FLG encodes the membrane receptor for aFGF. Further supporting evidence came from cross-linking experiments on intact cells with the covalent cross-linking agent disuccinimidyl suberate and 1251-labeled aFGF as a specific probe. The cross-linked '251-labeled aFGF-aFGF receptor complex was specifically immunoprecipitated with FLG antipeptide antibodies. It appears, therefore, that the receptor(s) for aFGF is related to the FLG gene product.Polypeptide growth factors mediate their mitogenic response by binding to and activating specific cell surface receptors.-A large family of growth factor receptors possess cytoplasmic domains with intrinsic protein tyrosine kinase activities (for reviews, see refs. 1-3). Mutational analysis has shown that the protein tyrosine kinase activity of these growth factor receptors is essential for signal transduction, mitogenesis, transformation, and normal cellular trafficking (for reviews, see refs. 1 and 2). The receptors containing protein tyrosine kinase activity include the receptors for insulin, insulin-like growth factor 1, epidermal growth factor, platelet-derived growth factor (PDGF), and colony-stimulating factor 1 (CSF-1) (1-3). It was also reported that the binding of eithier basic or acidic fibroblast growth factor (bFGF and aFGF, respectively) to their cell surface receptors elicited tyrosine phosphorylation of cellular substrates in living cells, suggesting that FGF receptors also belong to the tyrosine kinase receptor gene family (4, 5). FGFs are essentially ubiquitous in nature. High-affinity FGF receptors in the range of 110-150 kDa have been identified on a variety of cell types by chemical crosslinking (6)(7)(8)(9)(10)(11)(12)(13)(14). Low-affinity binding sites have also been described and appear to be glycosaminoglycans (14, 15). High-affinity FGF receptors are lost permanently during mouse skeletal muscle-cell terminal differentiation in vitro (16) and are reduced at high cell density (17). Further investigation of these phenomena would be greatly facilitated with molecular probes for studies of FGF receptor expression.In recent years tyrosine kinases were identified by a variety of approaches including the analysis of retroviral oncogenes, transformation of NIH 3T3 cells by transfection with DNA from human or animal tumors and by hybridization at low stringency of either cDNA or genomic libraries with DNA prob...

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Cell density regulates the number of cell surface receptors for fibroblast growth factor

Cited by 42 publications

References 9 publications

Differential Activation of Multiple Signalling Pathways Dictates eNOS Upregulation by FGF2 but not VEGF in Placental Artery Endothelial Cells

Differential Activation of Multiple Signalling Pathways Dictates eNOS Upregulation by FGF2 but not VEGF in Placental Artery Endothelial Cells

Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries.

Receptor for acidic fibroblast growth factor is related to the tyrosine kinase encoded by the fms-like gene (FLG).

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