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

Nat Immunol. 2006 Mar;7(3):274-83. doi: 10.1038/ni1310. Epub 2006 Feb 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Protein Phosphatase 2
  • DUSP2 protein, human
  • Dual Specificity Phosphatase 2
  • Dusp2 protein, mouse
  • Protein Tyrosine Phosphatases

Associated data

  • GEO/GSE3982