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dc.contributor.authorPlows, D
dc.contributor.authorBriassouli, P
dc.contributor.authorOwen, C
dc.contributor.authorZoumpourlis, V
dc.contributor.authorGarrett, MD
dc.contributor.authorPintzas, A
dc.date.accessioned2018-06-26T09:02:19Z
dc.date.issued2002-03
dc.identifier.citationThe Biochemical journal, 2002, 362 (Pt 2), pp. 305 - 315
dc.identifier.issn0264-6021
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1926
dc.identifier.eissn1470-8728
dc.identifier.doi10.1042/0264-6021:3620305
dc.description.abstractThe Ras family of GTP-binding proteins are key transducers of extracellular signals, particularly through the mitogen-activated protein kinase (MAPK) pathway. Constitutively active forms of Ras are found in a variety of tumours, suggesting an important role for this pathway in cancer. Here we report that initial cellular exposure to oncogenic Ras chronically activated the MAPK pathway in the cytoplasm, but transiently activated the same pathway in the nucleus. Nuclear-activated extracellular signal-regulated kinase (ERK) was rapidly dephosphorylated, with consequent short-term activation of the Elk-1 transcription factor and expression of the c-fos gene. Additional experiments suggested that the regulatory mechanism involved requires the calcium-dependent protein phosphotyrosine phosphatase MAPK phosphatase-1 (MKP-1). This is the first report on the ability of Ras, in the absence of growth factors, to transiently activate the MAPK pathway in the nucleus and show an involvement of MKP-1 in nuclear ERK2 regulation. In addition we show that transient activation of the MAPK pathway is sufficient to drive chronic cell-cycle progression. We conclude that, whereas the MAPK pathway is necessary to initiate cellular proliferation and transformation, the transient nature of the MAPK pathway activation suggests the involvement of additional signalling pathway(s) regulated by Ras.
dc.formatPrint
dc.format.extent305 - 315
dc.languageeng
dc.language.isoeng
dc.subject3T3 Cells
dc.subjectCell Nucleus
dc.subjectAnimals
dc.subjectMice
dc.subjectCell Transformation, Neoplastic
dc.subjectVanadates
dc.subjectEgtazic Acid
dc.subjectOkadaic Acid
dc.subjectEcdysone
dc.subjectMitogen-Activated Protein Kinases
dc.subjectMitogen-Activated Protein Kinase 1
dc.subjectMitogen-Activated Protein Kinase 3
dc.subjectCell Cycle Proteins
dc.subjectImmediate-Early Proteins
dc.subjectReproducibility of Results
dc.subjectAmino Acid Substitution
dc.subjectCell Cycle
dc.subjectCell Division
dc.subjectMAP Kinase Signaling System
dc.subjectEnzyme Activation
dc.subjectPhosphorylation
dc.subjectGenes, ras
dc.subjectPhosphoprotein Phosphatases
dc.subjectProtein Tyrosine Phosphatases
dc.subjectDual Specificity Phosphatase 1
dc.subjectProtein Phosphatase 1
dc.titleEcdysone-inducible expression of oncogenic Ha-Ras in NIH 3T3 cells leads to transient nuclear localization of activated extracellular signal-regulated kinase regulated by mitogen-activated protein kinase phosphatase-1.
dc.typeJournal Article
rioxxterms.versionofrecord10.1042/0264-6021:3620305
rioxxterms.licenseref.startdate2002-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe Biochemical journal
pubs.issuePt 2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Cell Cycle Control (including GCLP Biomarker Group)
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Cell Cycle Control (including GCLP Biomarker Group)
pubs.publication-statusPublished
pubs.volume362
pubs.embargo.termsNot known
icr.researchteamCell Cycle Control (including GCLP Biomarker Group)en_US
dc.contributor.icrauthorGarrett, Michelle Dawnen


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