A STAT-regulated, stress-induced signalling pathway in Dictyostelium.
The Dictyostelium stalk cell inducer differentiation-inducing factor (DIF) directs tyrosine phosphorylation and nuclear accumulation of the STAT (signal transducer and activator of transcription) protein Dd-STATc. We show that hyperosmotic stress, heat shock and oxidative stress also activate Dd-STATc. Hyperosmotic stress is known to elevate intracellular cGMP and cAMP levels, and the membrane-permeant analogue 8-bromo-cGMP rapidly activates Dd-STATc, whereas 8-bromo-cAMP is a much less effective inducer. Surprisingly, however, Dd-STATc remains stress activatable in null mutants for components of the known cGMP-mediated and cAMP-mediated stress-response pathways and in a double mutant affecting both pathways. Also, Dd-STATc null cells are not abnormally sensitive to hyperosmotic stress. Microarray analysis identified two genes, gapA and rtoA, that are induced by hyperosmotic stress. Osmotic stress induction of gapA and rtoA is entirely dependent on Dd-STATc. Neither gene is inducible by DIF but both are rapidly inducible with 8-bromo-cGMP. Again, 8-bromo-cAMP is a much less potent inducer than 8-bromo-cGMP. These data show that Dd-STATc functions as a transcriptional activator in a stress-response pathway and the pharmacological evidence, at least, is consistent with cGMP acting as a second messenger.
Araki
Tsuyoshi
T
School of Life Sciences, University of Dundee, Wellcome Trust Biocentre, Dow Street, Dundee, DD1 5EH, UK.
Tsujioka
Masatsune
M
Abe
Tomoaki
T
Fukuzawa
Masashi
M
Meima
Marcel
M
Schaap
Pauline
P
Morio
Takahiro
T
Urushihara
Hideko
H
Katoh
Mariko
M
Maeda
Mineko
M
Tanaka
Yoshimasa
Y
Takeuchi
Ikuo
I
Williams
Jeffrey G
JG
D021581:Active Transport, Cell Nucleus; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D009995:Osmosis; D018384:Oxidative Stress; D010766:Phosphorylation; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism / Q000502:physiology*; D050791:STAT Transcription Factors; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
D018797:Cell Cycle Proteins; D008164:Luminescent Proteins; D015800:Protozoan Proteins; C103074:RtoA protein, Dictyostelium discoideum; D050791:STAT Transcription Factors; C426825:STATc protein, Dictyostelium; D015534:Trans-Activators; D049452:Green Fluorescent Proteins; C016276:8-bromocyclic GMP; D014443:Tyrosine; D000242:Cyclic AMP; D006152:Cyclic GMP