dc.contributor.author | Jeffrey, Kate | |
dc.contributor.author | Brummer, Tilman | |
dc.contributor.author | Rolph, Michael | |
dc.contributor.author | Liu, Sue | |
dc.contributor.author | Callejas, Nuria | |
dc.contributor.author | Grumont, Raelene | |
dc.contributor.author | Gillieron, Corine | |
dc.contributor.author | Mackay, Fabienne | |
dc.contributor.author | Grey, Shane | |
dc.contributor.author | Camps, Montserrat | |
dc.contributor.author | Rommel, Christian | |
dc.contributor.author | Gerondakis, Steve | |
dc.contributor.author | Mackay, Charles R. | |
dc.date.accessioned | 2017-05-03T16:02:17Z | |
dc.date.available | 2017-05-03T16:02:17Z | |
dc.date.issued | 2006 | |
dc.date.modified | 2014-05-15T22:04:44Z | |
dc.identifier.issn | 15292908 | |
dc.identifier.doi | 10.1038/ni1310 | |
dc.identifier.uri | http://hdl.handle.net/10072/59137 | |
dc.description.abstract | Mitogen-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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Nature Publishing Group | |
dc.publisher.place | United States | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 274 | |
dc.relation.ispartofpageto | 283 | |
dc.relation.ispartofissue | 3 | |
dc.relation.ispartofjournal | Nature Immunology | |
dc.relation.ispartofvolume | 7 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Cellular Immunology | |
dc.subject.fieldofresearch | Immunology | |
dc.subject.fieldofresearchcode | 110704 | |
dc.subject.fieldofresearchcode | 1107 | |
dc.title | Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1 | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2006 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Rolph, Michael S. | |