Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts.
dc.contributor.author | Delehedde, Maryse | |
dc.contributor.author | Seve, Michel | |
dc.contributor.author | Sergeant, Nicolas | |
dc.contributor.author | Wartelle, Isabelle | |
dc.contributor.author | Lyon, Malcolm | |
dc.contributor.author | Rudland, Philip S | |
dc.contributor.author | Fernig, David G | |
dc.date.accessioned | 2010-01-19T16:40:28Z | |
dc.date.available | 2010-01-19T16:40:28Z | |
dc.date.issued | 2000-10-27 | |
dc.identifier.citation | Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts. 2000, 275 (43):33905-10 J. Biol. Chem. | en |
dc.identifier.issn | 0021-9258 | |
dc.identifier.pmid | 10944532 | |
dc.identifier.doi | 10.1074/jbc.M005949200 | |
dc.identifier.uri | http://hdl.handle.net/10541/90054 | |
dc.description.abstract | Fibroblast growth factor-2 (FGF-2) interacts with a dual receptor system consisting of tyrosine kinase receptors and heparan sulfate proteoglycans (HSPGs). In rat mammary fibroblasts, FGF-2 stimulated DNA synthesis and induced a sustained phosphorylation of p42/44(MAPK) and of its downstream target, p90(RSK). Moreover, FGF-2 also stimulated the transient degradation of IkappaBalpha and IkappaBbeta. PD098059, a specific inhibitor of p42/44(MAPK) phosphorylation, inhibited FGF-2-stimulated DNA synthesis, phosphorylation of p42/44(MAPK) and p90(RSK), and degradation of IkappaBbeta. In contrast, in chlorate-treated and hence sulfated glycosaminoglycan-deficient cells, FGF-2 was unable to stimulate DNA synthesis. However, FGF-2 was able to trigger a transient phosphorylation of both p42/44(MAPK) and p90(RSK), which peaked at 15 min and returned to control levels at 30 min. In these sulfated glycosaminoglycan-deficient cells, no degradation of IkappaBalpha and IkappaBbeta was observed after FGF-2 addition. However, in chlorate-treated cells, the addition of heparin or purified HSPGs simultaneously with FGF-2 restored DNA synthesis, the sustained phosphorylation of p42/44(MAPK) and p90(RSK), and the degradation of IkappaBalpha and IkappaBbeta. These results suggest that the HSPG receptor for FGF-2 not only influences the outcome of FGF-2 signaling, e.g. cell proliferation, but importantly regulates the immediate-early signals generated by this growth factor. | |
dc.language.iso | en | en |
dc.subject.mesh | Animals | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Female | |
dc.subject.mesh | Fibroblast Growth Factor 2 | |
dc.subject.mesh | Fibroblasts | |
dc.subject.mesh | Heparin | |
dc.subject.mesh | Heparitin Sulfate | |
dc.subject.mesh | I-kappa B Proteins | |
dc.subject.mesh | Mammary Glands, Animal | |
dc.subject.mesh | Mitogen-Activated Protein Kinase 1 | |
dc.subject.mesh | Mitogen-Activated Protein Kinase 3 | |
dc.subject.mesh | Mitogen-Activated Protein Kinases | |
dc.subject.mesh | Phosphorylation | |
dc.subject.mesh | Rats | |
dc.subject.mesh | Ribosomal Protein S6 Kinases | |
dc.title | Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts. | en |
dc.type | Article | en |
dc.contributor.department | School of Biological Sciences, Life Sciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom. | en |
dc.identifier.journal | The Journal of Biological Chemistry | en |
html.description.abstract | Fibroblast growth factor-2 (FGF-2) interacts with a dual receptor system consisting of tyrosine kinase receptors and heparan sulfate proteoglycans (HSPGs). In rat mammary fibroblasts, FGF-2 stimulated DNA synthesis and induced a sustained phosphorylation of p42/44(MAPK) and of its downstream target, p90(RSK). Moreover, FGF-2 also stimulated the transient degradation of IkappaBalpha and IkappaBbeta. PD098059, a specific inhibitor of p42/44(MAPK) phosphorylation, inhibited FGF-2-stimulated DNA synthesis, phosphorylation of p42/44(MAPK) and p90(RSK), and degradation of IkappaBbeta. In contrast, in chlorate-treated and hence sulfated glycosaminoglycan-deficient cells, FGF-2 was unable to stimulate DNA synthesis. However, FGF-2 was able to trigger a transient phosphorylation of both p42/44(MAPK) and p90(RSK), which peaked at 15 min and returned to control levels at 30 min. In these sulfated glycosaminoglycan-deficient cells, no degradation of IkappaBalpha and IkappaBbeta was observed after FGF-2 addition. However, in chlorate-treated cells, the addition of heparin or purified HSPGs simultaneously with FGF-2 restored DNA synthesis, the sustained phosphorylation of p42/44(MAPK) and p90(RSK), and the degradation of IkappaBalpha and IkappaBbeta. These results suggest that the HSPG receptor for FGF-2 not only influences the outcome of FGF-2 signaling, e.g. cell proliferation, but importantly regulates the immediate-early signals generated by this growth factor. |