Role for YakA, cAMP, and protein kinase A in regulation of stress responses of Dictyostelium discoideum cells.
The Dictyostelium protein kinase YakA is required for the growth-to-development transition. During growth YakA controls the cell cycle, regulating the intervals between cell divisions. When starved for nutrients Dictyostelium cells arrest growth and undergo changes in gene expression, decreasing vegetative mRNAs and inducing the expression of pkaC. YakA is an effector of these changes, being necessary for the decrease of vegetative mRNA expression and the increase of protein kinase A (PKA) activity that will ultimately regulate expression of adenylyl cyclase, cAMP synthesis, and the induction of development. We report a role for this kinase in the response to nitrosoative or oxidative stress of Dictyostelium cells. Hydrogen peroxide and sodium nitroprusside arrest the growth of cells and trigger cAMP synthesis and activation of PKA in a manner similar to the well-established response to nutrient starvation. We have found that yakA null cells are hypersensitive to nitrosoative/oxidative stress and that a second-site mutation in pkaC suppresses this sensitivity. The response to different stresses has been investigated and YakA, cAMP, and PKA have been identified as components of the pathway that regulate the growth arrest that follows treatment with compounds that generate reactive oxygen species. The effect of different types of stress was evaluated in Dictyostelium and the YakA/PKA pathway was also implicated in the response to heat stress.
Taminato
Alexandre
A
Instituto de Química, Departamento de Bioquímica, Universidade de São Paulo, São Paulo, Brazil 05508-900.
Bagattini
Raquel
R
Gorjão
Renata
R
Chen
Guokai
G
Kuspa
Adam
A
Souza
Glaucia Mendes
GM
D000818:Animals; D002455:Cell Division / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004023:Dictyostelium / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006358:Hot Temperature / Q000009:adverse effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D009599:Nitroprusside / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D011494:Protein Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology
D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D016877:Oxidants; D021122:Protein Subunits; C091861:spermine nitric oxide complex; D009599:Nitroprusside; D013096:Spermine; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D011494:Protein Kinases; C113280:YakA protein, Dictyostelium discoideum; D017868:Cyclic AMP-Dependent Protein Kinases