Periodic signaling controlled by an oscillatory circuit that includes protein kinases ERK2 and PKA.
Self-regulating systems often use robust oscillatory circuits. One such system controls the chemotactic signaling mechanism of Dictyostelium, where pulses of adenosine 3',5'-monophosphate (cAMP) are generated with a periodicity of 7 minutes. We have observed spontaneous oscillations in activation of the mitogen-activated protein (MAP) kinase ERK2 that occur in phase with peaks of cAMP, and we show that ERK2 modulates cAMP levels through the phosphodiesterase RegA. Computer modeling and simulations of the underlying circuit faithfully account for the ability of the cells to spontaneously generate periodic pulses during specific stages of development. Similar oscillatory processes may occur in cells of many different species.
Maeda
Mineko
M
Department of Biology, Graduate School of Science, Osaka University, Machikaneyama-cho 1-16, Toyonaka, Osaka 560-0043, Japan.
Lu
Sijie
S
Shaulsky
Gad
G
Miyazaki
Yuji
Y
Kuwayama
Hidekazu
H
Tanaka
Yoshimasa
Y
Kuspa
Adam
A
Loomis
William F
WF
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004023:Dictyostelium / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004789:Enzyme Activation; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D015398:Signal Transduction
D015800:Protozoan Proteins; D011953:Receptors, Cyclic AMP; C068125:cyclic AMP receptor cAR1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C112742:regA protein, Dictyostelium; D000262:Adenylyl Cyclases