title: Evidence that DIF-1 and hyper-osmotic stress activate a Dictyostelium STAT by inhibiting a specific protein tyrosine phosphatase.
abstract: 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.
authors.affiliation: University of Dundee, College of Life Sciences, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Araki
authors.forename: Judith
authors.initials: J
authors.lastname: Langenick
authors.forename: Marianne
authors.initials: M
authors.lastname: Gamper
authors.forename: Richard A
authors.initials: RA
authors.lastname: Firtel
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Williams
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D006588:Hexanones / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D009997:Osmotic Pressure; D018384:Oxidative Stress; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006588:Hexanones; D015800:Protozoan Proteins; D050791:STAT Transcription Factors; C426825:STATc protein, Dictyostelium; C053433:1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone; D017027:Protein Tyrosine Phosphatases