Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1
- Author(s)
- Jeffrey, KL; Brummer, T; Rolph, MS; Liu, SM; Callejas, NA; Grumont, RJ; Gillieron, C; Mackay, F; Grey, S; Camps, M; Rommel, C; Gerondakis, SD; Mackay, CR;
- Details
- Publication Year 2006-03,Volume 7,Issue #3,Page 274-283
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- PROTEIN-KINASE PHOSPHATASE-1; DUAL-SPECIFICITY PHOSPHATASE; TUMOR-NECROSIS-FACTOR; MAP KINASE; INDUCED ARTHRITIS; MAST-CELLS; CROSS-TALK; IN-VIVO; ACTIVATION; GENE
- Publisher's Version
- https://doi.org/10.1038/ni1310
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-03-01 12:00:00