title: Perturbations of the actin cytoskeleton activate a Dictyostelium STAT signalling pathway.
abstract: The Dictyostelium transcription factor STATc is tyrosine phosphorylated and accumulates in the nucleus when cells are exposed either to hyper-osmotic stress or to the prestalk-inducing polyketide DIF-1. In the case of stress STAT activation is mediated by regulated dephosphorylation; whereby two serine residues on PTP3, the tyrosine phosphatase that de-activates STATc, become phosphorylated after exposure to stress so inhibiting enzymatic activity. We now show that the more highly regulated of the two PTP3 serine residues, S747, is also phosphorylated in response to DIF-1, suggesting a common activation mechanism. Hyper-osmotic stress causes a re-distribution of F-actin to the cortex, cell rounding and shrinkage and we show that DIF-1 induces a similar but transient F-actin re-distribution and rounding response. We also find that two mechanistically distinct inhibitors of actin polymerization, latrunculin A and cytochalasin A induce phosphorylation at S747 of PTP3 and activate STATc. We suggest that PTP3 phosphorylation, and consequent STATc activation, are regulated by changes in F-actin polymerization status during stress and DIF-induced cytoskeletal remodelling.
authors.affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dow St., Dundee DD1 5EH, United Kingdom.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Araki
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Williams
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000378:metabolism*; D006588:Hexanones / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D015800:Protozoan Proteins / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000199:Actins; 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; D019703:Calcineurin