Our hosting provider will be performing UPS maintenance on Tuesday, Oct 25, 2016 between 8 AM and 5 PM PDT. SciCrunch searching services will be down during this time.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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.

Pubmed ID: 16474395


  • 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


Nature immunology

Publication Data

March 16, 2006

Associated Grants


Mesh Terms

  • Animals
  • Arthritis, Experimental
  • Dual Specificity Phosphatase 2
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Inflammation
  • Leukocytes
  • MAP Kinase Kinase 4
  • Mice
  • Mitogen-Activated Protein Kinases
  • Polymerase Chain Reaction
  • Protein Phosphatase 2
  • Protein Tyrosine Phosphatases
  • Receptor Cross-Talk