Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.0030218
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dc.titleA RNA Interference Screen Identifies the Protein Phosphatase 2A Subunit PR55γ as a Stress-Sensitive Inhibitor of c-SRC
dc.contributor.authorEichhorn P.J.A.
dc.contributor.authorCreyghton M.P.
dc.contributor.authorWilhelmsen K.
dc.contributor.authorVan Dam H.
dc.contributor.authorBernards R.
dc.date.accessioned2020-03-18T05:53:35Z
dc.date.available2020-03-18T05:53:35Z
dc.date.issued2007
dc.identifier.citationEichhorn P.J.A., Creyghton M.P., Wilhelmsen K., Van Dam H., Bernards R. (2007). A RNA Interference Screen Identifies the Protein Phosphatase 2A Subunit PR55γ as a Stress-Sensitive Inhibitor of c-SRC. PLoS Genetics 3 (12) : 2381-2394. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.0030218
dc.identifier.issn15537390
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165612
dc.description.abstractProtein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogene-induced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55γ and PR55δ as inhibitors of c-Jun NH2-terminal kinase (JNK) activation by UV irradiation. We show that PR55γ binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55γ and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55γ. © 2007 Eichhorn et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectmitogen activated protein kinase
dc.subjectphosphoprotein phosphatase inhibitor
dc.subjectpr 55 delta
dc.subjectpr55 gamma
dc.subjectserine
dc.subjectunclassified drug
dc.subjectCSK protein, human
dc.subjectoncoprotein
dc.subjectphosphoprotein phosphatase 2
dc.subjectPPP2R2C protein, human
dc.subjectprimer DNA
dc.subjectprotein tyrosine kinase
dc.subjectstress activated protein kinase
dc.subjectarticle
dc.subjectdrug inhibition
dc.subjectenzyme activity
dc.subjectgene control
dc.subjectgene repression
dc.subjecthuman
dc.subjectoncogene
dc.subjectphosphorylation
dc.subjectprotein analysis
dc.subjectprotein protein interaction
dc.subjectRNA interference
dc.subjectultraviolet irradiation
dc.subjectamino acid substitution
dc.subjectapoptosis
dc.subjectcell line
dc.subjectchemistry
dc.subjectdrug antagonism
dc.subjectenzyme activation
dc.subjectgenetic transfection
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectnucleotide sequence
dc.subjectphysiology
dc.subjectradiation exposure
dc.subjectsignal transduction
dc.subjectsite directed mutagenesis
dc.subjectultraviolet radiation
dc.subjectAmino Acid Substitution
dc.subjectApoptosis
dc.subjectBase Sequence
dc.subjectCell Line
dc.subjectDNA Primers
dc.subjectEnzyme Activation
dc.subjectHumans
dc.subjectJNK Mitogen-Activated Protein Kinases
dc.subjectMutagenesis, Site-Directed
dc.subjectPhosphorylation
dc.subjectProtein Phosphatase 2
dc.subjectProtein-Tyrosine Kinases
dc.subjectProto-Oncogene Proteins
dc.subjectRNA Interference
dc.subjectSerine
dc.subjectSignal Transduction
dc.subjectTransfection
dc.subjectUltraviolet Rays
dc.typeArticle
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.1371/journal.pgen.0030218
dc.description.sourcetitlePLoS Genetics
dc.description.volume3
dc.description.issue12
dc.description.page2381-2394
dc.published.statePublished
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