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dc.contributor.authorFinlay, Daviden
dc.date.accessioned2011-11-02T12:08:20Z
dc.date.available2011-11-02T12:08:20Z
dc.date.issued2009en
dc.date.submitted2009en
dc.identifier.citationFinlay DK., Sinclair LV., Fejoo C., Waugh C., Hagenbeek TJ., Spits H., Cantrell DA., Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes, Journal of Experimental Medcine, 206, 11, 2009, 2441 - 2454en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/60444
dc.descriptionPUBLISHEDen
dc.description.abstractIn normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)-mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study has characterized the role of PDK1 in the pathology caused by deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN). PDK1 is shown to be essential for lymphomagenesis caused by deletion of PTEN in T cell progenitors. However, PTEN deletion bypasses the normal PDK1-controlled signaling pathways that determine thymocyte growth and proliferation. PDK1 does have important functions in PTEN-null thymocytes, notably to control the PKB-Foxo signaling axis and to direct the repertoire of adhesion and chemokine receptors expressed by PTEN-null T cells. The results thus provide two novel insights concerning pathological signaling caused by PTEN loss in lymphocytes. First, PTEN deletion bypasses the normal PDK1-controlled metabolic checkpoints that determine cell growth and proliferation. Second, PDK1 determines the cohort of chemokine and adhesion receptors expressed by PTEN-null cells, thereby controlling their migratory capacity.en
dc.description.sponsorshipThis work was supported by a Welcome Trust Principal Research Fellowship and Program Grant (065975/Z/01/A).en
dc.format.extent2441en
dc.format.extent2454en
dc.language.isoenen
dc.relation.ispartofseriesJournal of Experimental Medcineen
dc.relation.ispartofseries206en
dc.relation.ispartofseries11en
dc.rightsYen
dc.subjectImmunologyen
dc.subjectT cellsen
dc.titlePhosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytesen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/finlayden
dc.identifier.rssinternalid75185en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.rssurihttp://dx.crossref.org/10.1084%2Fjem.20090219en
dc.identifier.orcid_id0000-0003-2716-6679en


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