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dc.contributor.authorJeffrey, Kate
dc.contributor.authorBrummer, Tilman
dc.contributor.authorRolph, Michael
dc.contributor.authorLiu, Sue
dc.contributor.authorCallejas, Nuria
dc.contributor.authorGrumont, Raelene
dc.contributor.authorGillieron, Corine
dc.contributor.authorMackay, Fabienne
dc.contributor.authorGrey, Shane
dc.contributor.authorCamps, Montserrat
dc.contributor.authorRommel, Christian
dc.contributor.authorGerondakis, Steve
dc.contributor.authorMackay, Charles R.
dc.date.accessioned2017-05-03T16:02:17Z
dc.date.available2017-05-03T16:02:17Z
dc.date.issued2006
dc.date.modified2014-05-15T22:04:44Z
dc.identifier.issn15292908
dc.identifier.doi10.1038/ni1310
dc.identifier.urihttp://hdl.handle.net/10072/59137
dc.description.abstractMitogen-activated protein kinases facilitate many cellular processes and are essential for immune cell function. Their activity is controlled by kinases and dual-specificity phosphatases. A comprehensive microarray analysis of human leukocytes identified DUSP2 (encoding the phosphatase PAC-1) as one of the most highly induced transcripts in activated immune cells. We generated Dusp2-/- mice and found considerably reduced inflammatory responses in the 'K/BxN' model of rheumatoid arthritis. PAC-1 deficiency led to increased activity of Jun kinase (Jnk) but unexpected impairment of the activity of extracellular signal-regulated kinase (Erk) and the kinase p38, reduced activity of the transcription factor Elk1 and a complex of mobilized transcription factor NFAT and the AP-1 transcription factor and decreased effector immune cell function. Thus, PAC-1 is a key positive regulator of inflammatory cell signaling and effector functions, mediated through Jnk and Erk mitogen-activated protein kinase crosstalk.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom274
dc.relation.ispartofpageto283
dc.relation.ispartofissue3
dc.relation.ispartofjournalNature Immunology
dc.relation.ispartofvolume7
dc.rights.retentionY
dc.subject.fieldofresearchCellular Immunology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchcode110704
dc.subject.fieldofresearchcode1107
dc.titlePositive regulation of immune cell function and inflammatory responses by phosphatase PAC-1
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2006
gro.hasfulltextNo Full Text
gro.griffith.authorRolph, Michael S.


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