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

    Author(s)
    Jeffrey, Kate
    Brummer, Tilman
    Rolph, Michael
    Liu, Sue
    Callejas, Nuria
    Grumont, Raelene
    Gillieron, Corine
    Mackay, Fabienne
    Grey, Shane
    Camps, Montserrat
    Rommel, Christian
    Gerondakis, Steve
    Mackay, Charles R.
    Griffith University Author(s)
    Rolph, Michael S.
    Year published
    2006
    Metadata
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    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 ...
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    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.
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    Journal Title
    Nature Immunology
    Volume
    7
    Issue
    3
    DOI
    https://doi.org/10.1038/ni1310
    Subject
    Cellular Immunology
    Immunology
    Publication URI
    http://hdl.handle.net/10072/59137
    Collection
    • Journal articles

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