Evidence that DIF-1 and hyper-osmotic stress activate a Dictyostelium STAT by inhibiting a specific protein tyrosine phosphatase

Tsuyoshi Araki, Judith Langenick, Marianne Gamper, Richard A. Firtel, Jeffrey G. Williams (Lead / Corresponding author)

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    22 Citations (Scopus)


    STATc becomes tyrosine phosphorylated and accumulates in the nucleus when Dictyostelium cells are exposed to the prestalk cell inducer Differentiation inducing factor 1 (DIF-1), or are subjected to hyper-osmotic stress. We show that the protein tyrosine phosphatase PTP3 interacts directly with STATc and that STATc is refractory to activation in PTP3 overexpressing cells. Conversely, overexpression of a dominant inhibitor of PTP3 leads to constitutive tyrosine phosphorylation and ectopic nuclear localisation of STATc. Treatment of cells with DIF-1 or exposure to hyper-osmotic stress induces a decrease in biochemically assayable PTP3 activity and both agents also induce serine-threonine phosphorylation of PTP3. These observations suggest a novel mode of STAT activation, whereby serine-threonine phosphorylation of a cognate protein tyrosine phosphatase results in the inhibition of its activity, shifting the phosphorylation-dephosphorylation equilibrium in favour of phosphorylation.

    Original languageEnglish
    Pages (from-to)1347-1353
    Number of pages7
    Issue number7
    Publication statusPublished - 1 Apr 2008


    • STAT
    • Dictyostelium
    • Tyrosine phosphatase
    • Stress
    • DIF-1
    • Nuclear translocation
    • Osmotic shock
    • Phosphorylation
    • Pathway
    • Differentiation
    • Substrate
    • Growth
    • Identification
    • Expression
    • Discoideum

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