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Eukaryotic Cell, March 2009, p. 388-397, Vol. 8, No. 3
1535-9778/09/$08.00+0     doi:10.1128/EC.00334-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Functional Analysis of Protein Kinase CK2 of the Human Malaria Parasite Plasmodium falciparum{triangledown} ,{dagger}

Zoë Holland,1 Renaud Prudent,2,3 Jean-Baptiste Reiser,4,5 Claude Cochet,2,3 and Christian Doerig1,6*

INSERM U609, Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom,1 INSERM U873, Grenoble F-38054, France,2 Université Joseph Fourier, Grenoble, France,3 CEA, iRTSV/LTS, Grenoble, F-38054, France,4 CNRS, CEA, IBS/LCCP, Grenoble, France,5 INSERM U609, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland6

Received 3 October 2008/ Accepted 9 December 2008

Protein kinase CK2 (casein kinase 2) is a eukaryotic serine/threonine protein kinase with multiple substrates and roles in diverse cellular processes, including differentiation, proliferation, and translation. The mammalian holoenzyme consists of two catalytic alpha or alpha' subunits and two regulatory beta subunits. We report the identification and characterization of a Plasmodium falciparum CK2{alpha} orthologue, PfCK2{alpha}, and two PfCK2β orthologues, PfCK2β1 and PfCK2β2. Recombinant PfCK2{alpha} possesses protein kinase activity, exhibits similar substrate and cosubstrate preferences to those of CK2{alpha} subunits from other organisms, and interacts with both of the PfCK2β subunits in vitro. Gene disruption experiments show that the presence of PfCK2{alpha} is crucial to asexual blood stage parasites and thereby validate the enzyme as a possible drug target. PfCK2{alpha} is amenable to inhibitor screening, and we report differential susceptibility between the human and P. falciparum CK2{alpha} enzymes to a small molecule inhibitor. Taken together, our data identify PfCK2{alpha} as a potential target for antimalarial chemotherapeutic intervention.

* Corresponding author. Mailing address: INSERM U609, Global Health Institute, EPFL-SV-GHI, Station 19, CH-1015 Lausanne, Switzerland. Phone: 41 21 693 0983. E-mail: christian.doerig{at}epfl.ch

{triangledown} Published ahead of print on 29 December 2008.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, March 2009, p. 388-397, Vol. 8, No. 3
1535-9778/09/$08.00+0     doi:10.1128/EC.00334-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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