Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1
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
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