Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1
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.
|Authors||Jeffrey, K. L.;Brummer, T.;Rolph, M. S.;Liu, S. M.;Callejas, N. A.;Grumont, R. J.;Gillieron, C.;Mackay, F.;Grey, S.;Camps, M.;Rommel, C.;Gerondakis, S. D.;Mackay, C. R. :|
|Publisher Name||NAT IMMUNOL|
|Published Date||2006-01-01 00:00:00|
|OpenAccess Link||https://publications.gimr.garvan.org.au/download.php?2068_10574/06 Jeffrey Nat Imm.pdf|