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PNAS 99 (24): 15788-15793

Copyright © 2002 by the National Academy of Sciences.

Nonlinear partial differential equations and applications


KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria

Hideo Iwasaki*,{dagger}, Taeko Nishiwaki*, Yohko Kitayama, Masato Nakajima, and Takao Kondo{dagger}

Division of Biological Science, Graduate School of Science, Nagoya University, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Furo-cho, Chikusa, Nagoya 464-8602, Japan

Received for publication August 5, 2002.

Abstract: Cyanobacterial clock proteins KaiA and KaiC are proposed as positive and negative regulators in the autoregulatory circadian kaiBC expression, respectively. Here, we show that activation of kaiBC expression by kaiA requires KaiC, suggesting a positive feedback control in the cyanobacterial clockwork. We found that robust circadian phosphorylation of KaiC. KaiA was essential for in vivo KaiC phosphorylation and activated in vitro KaiC autophosphorylation. These effects of KaiA were attenuated by the kaiA2 long period mutation. Both the long period phenotype and the abnormal KaiC phosphorylation in this mutant were suppressed by a previously undocumented kaiC mutation. We propose that KaiA-stimulated circadian KaiC phosphorylation is important for circadian timing.

* H.I. and T.N. contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: iwasaki{at} or kondo{at}

Edited by Robert Haselkorn, University of Chicago, Chicago, IL, and approved September 12, 2002

This paper was submitted directly (Track II) to the PNAS office.

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