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Article: Phosphorylation of nuclear phospholipase C β1 by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor I

TitlePhosphorylation of nuclear phospholipase C β1 by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor I
Authors
Issue Date2001
Citation
Molecular And Cellular Biology, 2001, v. 21 n. 9, p. 2981-2990 How to Cite?
AbstractIt is well established that a phosphoinositide (PI) cycle which is operationally distinct from the classical plasma membrane PI cycle exists within the nucleus, where it is involved in both cell proliferation and differentiation. However, little is known about the regulation of the nuclear PI cycle. Here, we report that nucleus-localized phospholipase C (PLC) β1, the key enzyme for the initiation of this cycle, is a physiological target of extracellular signal-regulated kinase (ERK). Stimulation of Swiss 3T3 cells with insulin-like growth factor I (IGF-I) caused rapid nuclear translocation of activated ERK and concurrently induced phosphorylation of nuclear PLC β1, which was completely blocked by the MEK inhibitor PD 98059. Coimmunoprecipitation detected a specific association between the activated ERK and PLC β1 within the nucleus. In vitro studies revealed that recombinant PLC β1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by PKA. The ERK phosphorylation site was mapped to serine 982, which lies within a PSSP motif located in the characteristic carboxy-terminal tail of PLC β1. In cells overexpressing a PLC β1 mutant in which serine 982 is replaced by glycine (S982G), IGF-I failed to activate the nuclear PI cycle, and its mitogenic effect was also markedly attenuated. Expression of S982G was found to inhibit ERK-mediated phosphorylation of endogenous PLC β1. This result suggests that ERK-evoked phosphorylation of PLC β1 at serine 982 plays a critical role in the activation of the nuclear PI cycle and is also crucial to the mitogenic action of IGF-I.
Persistent Identifierhttp://hdl.handle.net/10722/162498
ISSN
2015 Impact Factor: 4.427
2015 SCImago Journal Rankings: 3.806
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXu, Aen_US
dc.contributor.authorSuh, PGen_US
dc.contributor.authorMarmyConus, Nen_US
dc.contributor.authorPearson, RBen_US
dc.contributor.authorOh Yong Seoken_US
dc.contributor.authorCocco, Len_US
dc.contributor.authorGilmour, RSen_US
dc.date.accessioned2012-09-05T05:20:32Z-
dc.date.available2012-09-05T05:20:32Z-
dc.date.issued2001en_US
dc.identifier.citationMolecular And Cellular Biology, 2001, v. 21 n. 9, p. 2981-2990en_US
dc.identifier.issn0270-7306en_US
dc.identifier.urihttp://hdl.handle.net/10722/162498-
dc.description.abstractIt is well established that a phosphoinositide (PI) cycle which is operationally distinct from the classical plasma membrane PI cycle exists within the nucleus, where it is involved in both cell proliferation and differentiation. However, little is known about the regulation of the nuclear PI cycle. Here, we report that nucleus-localized phospholipase C (PLC) β1, the key enzyme for the initiation of this cycle, is a physiological target of extracellular signal-regulated kinase (ERK). Stimulation of Swiss 3T3 cells with insulin-like growth factor I (IGF-I) caused rapid nuclear translocation of activated ERK and concurrently induced phosphorylation of nuclear PLC β1, which was completely blocked by the MEK inhibitor PD 98059. Coimmunoprecipitation detected a specific association between the activated ERK and PLC β1 within the nucleus. In vitro studies revealed that recombinant PLC β1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by PKA. The ERK phosphorylation site was mapped to serine 982, which lies within a PSSP motif located in the characteristic carboxy-terminal tail of PLC β1. In cells overexpressing a PLC β1 mutant in which serine 982 is replaced by glycine (S982G), IGF-I failed to activate the nuclear PI cycle, and its mitogenic effect was also markedly attenuated. Expression of S982G was found to inhibit ERK-mediated phosphorylation of endogenous PLC β1. This result suggests that ERK-evoked phosphorylation of PLC β1 at serine 982 plays a critical role in the activation of the nuclear PI cycle and is also crucial to the mitogenic action of IGF-I.en_US
dc.languageengen_US
dc.relation.ispartofMolecular and Cellular Biologyen_US
dc.subject.mesh3T3 Cellsen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Nucleus - Enzymologyen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshInsulin-Like Growth Factor I - Metabolism - Pharmacologyen_US
dc.subject.meshIsoenzymes - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMitogen-Activated Protein Kinase 1 - Metabolismen_US
dc.subject.meshMitogen-Activated Protein Kinase 3en_US
dc.subject.meshMitogen-Activated Protein Kinases - Metabolismen_US
dc.subject.meshMitogens - Metabolism - Pharmacologyen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshPhospholipase C Betaen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshSerine - Genetics - Metabolismen_US
dc.subject.meshSpodoptera - Cytologyen_US
dc.subject.meshType C Phospholipases - Genetics - Metabolismen_US
dc.titlePhosphorylation of nuclear phospholipase C β1 by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor Ien_US
dc.typeArticleen_US
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_US
dc.identifier.authorityXu, A=rp00485en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/MCB.21.9.2981-2990.2001en_US
dc.identifier.pmid11287604-
dc.identifier.scopuseid_2-s2.0-0035052817en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035052817&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume21en_US
dc.identifier.issue9en_US
dc.identifier.spage2981en_US
dc.identifier.epage2990en_US
dc.identifier.isiWOS:000168092600002-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridXu, A=7202655409en_US
dc.identifier.scopusauthoridSuh, PG=7004546064en_US
dc.identifier.scopusauthoridMarmyConus, N=6508233912en_US
dc.identifier.scopusauthoridPearson, RB=7401904914en_US
dc.identifier.scopusauthoridOh Yong Seok=7409714058en_US
dc.identifier.scopusauthoridCocco, L=7007037315en_US
dc.identifier.scopusauthoridGilmour, RS=7102979590en_US

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