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Originally published In Press as doi:10.1074/jbc.M601914200 on June 29, 2006

J. Biol. Chem., Vol. 281, Issue 37, 27126-27133, September 15, 2006
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PfPKB, a Protein Kinase B-like Enzyme from Plasmodium falciparum

II. IDENTIFICATION OF CALCIUM/CALMODULIN AS ITS UPSTREAM ACTIVATOR AND DISSECTION OF A NOVEL SIGNALING PATHWAY*

Ankush Vaid1 and Pushkar Sharma2

From the Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India

Intracellular cell signaling cascades of protozoan parasite Plasmodium falciparum are not clearly understood. We have reported previously (Kumar, A., Vaid, A., Syin, C., and Sharma, P. (2004) J. Biol. Chem. 279, 24255–24264) the identification and characterization of a protein kinase B-like enzyme in P. falciparum (PfPKB). PfPKB lacks the phosphoinositide-interacting pleckstrin homology domain present in mammalian protein kinase B. Therefore, the mechanism of PfPKB regulation was expected to be different from that of the host and had remained unknown. We have identified calmodulin (CaM) as the regulator of PfPKB activity. A CaM binding domain was mapped in the N-terminal region of PfPKB. CaM, in a calcium-dependent manner, interacts with this domain and activates PfPKB. CaM associates with PfPKB in the parasite and regulates its activity. Furthermore phospholipase C acts as an upstream regulator of this cascade as it facilitates the release of calcium from intracellular stores. This is one of the first multicomponent signaling pathways to be dissected in the malaria parasite.


Received for publication, February 28, 2006 , and in revised form, June 29, 2006.

* This work was supported in part by a senior research fellowship (to P. S.) from The Wellcome Trust, UK and by intramural funding from the Department of Biotechnology, New Delhi to National Institute of Immunology. Paper I in this series is Ref. 1. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 A junior research fellow of Council of Scientific and Industrial Research, New Delhi.

2 To whom correspondence should be addressed. Tel.: 91-11-26717123 (ext. 791); Fax: 91-11-26162125; E-mail: pushkar{at}nii.res.in.


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A. Vaid, D. C. Thomas, and P. Sharma
Role of Ca2+/Calmodulin-PfPKB Signaling Pathway in Erythrocyte Invasion by Plasmodium falciparum
J. Biol. Chem., February 29, 2008; 283(9): 5589 - 5597.
[Abstract] [Full Text] [PDF]




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