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dc.contributor.authorDelehedde, Maryse
dc.contributor.authorSeve, Michel
dc.contributor.authorSergeant, Nicolas
dc.contributor.authorWartelle, Isabelle
dc.contributor.authorLyon, Malcolm
dc.contributor.authorRudland, Philip S
dc.contributor.authorFernig, David G
dc.date.accessioned2010-01-19T16:40:28Z
dc.date.available2010-01-19T16:40:28Z
dc.date.issued2000-10-27
dc.identifier.citationFibroblast 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.issn0021-9258
dc.identifier.pmid10944532
dc.identifier.doi10.1074/jbc.M005949200
dc.identifier.urihttp://hdl.handle.net/10541/90054
dc.description.abstractFibroblast 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.isoenen
dc.subject.meshAnimals
dc.subject.meshCells, Cultured
dc.subject.meshDNA
dc.subject.meshFemale
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshFibroblasts
dc.subject.meshHeparin
dc.subject.meshHeparitin Sulfate
dc.subject.meshI-kappa B Proteins
dc.subject.meshMammary Glands, Animal
dc.subject.meshMitogen-Activated Protein Kinase 1
dc.subject.meshMitogen-Activated Protein Kinase 3
dc.subject.meshMitogen-Activated Protein Kinases
dc.subject.meshPhosphorylation
dc.subject.meshRats
dc.subject.meshRibosomal Protein S6 Kinases
dc.titleFibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts.en
dc.typeArticleen
dc.contributor.departmentSchool of Biological Sciences, Life Sciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom.en
dc.identifier.journalThe Journal of Biological Chemistryen
html.description.abstractFibroblast 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.


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