Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

Solyakov, L. et al. (2011) Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum. Nature Communications, 2, 565. (doi: 10.1038/ncomms1558) (PMID:22127061)

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Abstract

The role of protein phosphorylation in the life cycle of malaria parasites is slowly emerging. Here we combine global phospho-proteomic analysis with kinome-wide reverse genetics to assess the importance of protein phosphorylation in Plasmodium falciparum asexual proliferation. We identify 1177 phosphorylation sites on 650 parasite proteins that are involved in a wide range of general cellular activities such as DNA synthesis, transcription and metabolism as well as key parasite processes such as invasion and cyto-adherence. Several parasite protein kinases are themselves phosphorylated on putative regulatory residues, including tyrosines in the activation loop of PfGSK3 and PfCLK3; we show that phosphorylation of PfCLK3 Y526 is essential for full kinase activity. A kinome-wide reverse genetics strategy identified 36 parasite kinases as likely essential for erythrocytic schizogony. These studies not only reveal processes that are regulated by protein phosphorylation, but also define potential anti-malarial drug targets within the parasite kinome.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tobin, Andrew and Alam, Dr Mahmood
Authors: Solyakov, L., Halbert, J., Alam, M. M., Semblat, J.-P., Dorin-Semblat, D., Reininger, L., Bottrill, A. R., Mistry, S., Abdi, A., Fennell, C., Holland, Z., Demarta, C., Bouza, Y., Sicard, A., Nivez, M.-P., Eschenlauer, S., Lama, T., Thomas, D. C., Sharma, P., Agarwal, S., Kern, S., Pradel, G., Graciotti, M., Tobin, A. B., and Doerig, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2011 Macmillan Publishers Limited
First Published:First published in Nature Communications 2: 565
Publisher Policy:Reproduced under a Creative Commons License

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