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

被引：213

作者：

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 ^{[1
]}

机构：

[1] Garvan Inst Med Res, Sydney, NSW 2010, Australia

[2] Cooperat Res Ctr Asthma, Sydney, NSW 2010, Australia

[3] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

[4] Serono Int, Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland

来源：

NATURE IMMUNOLOGY | 2006年 / 7卷 / 03期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ni1310

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：274 / 283

页数：10