Osmotic stress response in Dictyostelium is mediated by cAMP.
DokA, a homolog of bacterial hybrid histidine kinases, is essential for hyperosmotic stress resistance in Dictyostelium: We show that a transient intracellular cAMP signal, dependent on the presence of DokA, is generated in response to an osmotic shock. This variation of cAMP levels contributes to survival under hypertonic conditions. In contrast to the low cAMP levels observed in dokA(-) strains, overexpression of the receiver domain of DokA causes an increase in cAMP levels, resulting in a rapidly developing phenotype. We present biochemical and cell biological data indicating that the DokA receiver domain is a dominant-negative regulator of a phosphorelay, which controls the intracellular cAMP phosphodiesterase RegA. The activity of the DokA receiver domain depends on a conserved aspartate, mutation of which reverses the developmental phenotype, as well as the deregulation of cAMP metabolism.
Ott
A
A
Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany.
Oehme
F
F
Keller
H
H
Schuster
S C
SC
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015870:Gene Expression; D009997:Osmotic Pressure; D010641:Phenotype; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction
D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; C112741:RdeA protein, Dictyostelium; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C101159:DokA protein, Dictyostelium discoideum; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C112742:regA protein, Dictyostelium