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

TY - JOUR

T1 - Evidence that DIF-1 and hyper-osmotic stress activate a Dictyostelium STAT by inhibiting a specific protein tyrosine phosphatase

AU - Araki, Tsuyoshi

AU - Langenick, Judith

AU - Gamper, Marianne

AU - Firtel, Richard A.

AU - Williams, Jeffrey G.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - 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.

AB - 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.

KW - STAT

KW - Dictyostelium

KW - Tyrosine phosphatase

KW - Stress

KW - DIF-1

KW - Nuclear translocation

KW - Osmotic shock

KW - Phosphorylation

KW - Pathway

KW - Differentiation

KW - Substrate

KW - Growth

KW - Identification

KW - Expression

KW - Discoideum

UR - https://www.scopus.com/pages/publications/43049124400

U2 - 10.1242/dev.009936

DO - 10.1242/dev.009936

M3 - Article

C2 - 18305004

SN - 0950-1991

VL - 135

SP - 1347

EP - 1353

JO - Development

JF - Development

IS - 7

ER -