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First published online 27 May 2003
doi: 10.1242/jcs.00501

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A STAT-regulated, stress-induced signalling pathway in Dictyostelium

Tsuyoshi Araki^1,*, Masatsune Tsujioka^1,*, Tomoaki Abe¹, Masashi Fukuzawa¹, Marcel Meima¹, Pauline Schaap¹, Takahiro Morio², Hideko Urushihara², Mariko Katoh², Mineko Maeda³, Yoshimasa Tanaka², Ikuo Takeuchi⁴ and Jeffrey G. Williams^1,

¹ School of Life Sciences, University of Dundee, Wellcome Trust Biocentre, Dow Street, Dundee, DD1 5EH, UK
² Institute of Biological Sciences, University of Tsukuba,Tsukuba, Ibaraki 305-8572, Japan
³ Department of Biology, Osaka University, Machikaneyama 1-16, Toyonaka, Osaka 560-0043, Japan
⁴ Novartis Foundation (Japan) for the Promotion of Science, Roppongi, Minato-ku, Tokyo 106-0032, Japan

Author for correspondence (e-mail: j.g.williams{at}dundee.ac.uk)

Accepted 24 March 2003

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.

Key words: Dictyostelium, DIF, STAT, Stress response

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