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Science 304 (5672): 875-878

Copyright © 2004 by the American Association for the Advancement of Science

Periodic Signaling Controlled by an Oscillatory Circuit That Includes Protein Kinases ERK2 and PKA

Mineko Maeda,1 Sijie Lu,2* Gad Shaulsky,3 Yuji Miyazaki,1 Hidekazu Kuwayama,4 Yoshimasa Tanaka,4 Adam Kuspa,2,3 William F. Loomis5{dagger}

Abstract: 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.

1 Department of Biology, Graduate School of Science, Osaka University, Machikaneyama-cho 1-16, Toyonaka, Osaka 560-0043, Japan.
2 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston TX 77030, USA.
3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX 77030, USA.
4 Institute of Biological Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
5 Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.

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* Present address: Department of Blood and Marrow Transplantation, M. D. Anderson Cancer Center, Houston, TX 77030, USA.

{dagger} To whom correspondence should be addressed. E-mail: wloomis{at}

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