Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90054
Title:
Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts.
Authors:
Delehedde, Maryse; Seve, Michel; Sergeant, Nicolas; Wartelle, Isabelle; Lyon, Malcolm; Rudland, Philip S; Fernig, David G
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.
Affiliation:
School of Biological Sciences, Life Sciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom.
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.
Journal:
The Journal of Biological Chemistry
Issue Date:
27-Oct-2000
URI:
http://hdl.handle.net/10541/90054
DOI:
10.1074/jbc.M005949200
PubMed ID:
10944532
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDelehedde, Maryseen
dc.contributor.authorSeve, Michelen
dc.contributor.authorSergeant, Nicolasen
dc.contributor.authorWartelle, Isabelleen
dc.contributor.authorLyon, Malcolmen
dc.contributor.authorRudland, Philip Sen
dc.contributor.authorFernig, David Gen
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.en
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
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