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)
|
Text
194775.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. 1MB |
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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
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 |
University Staff: Request a correction | Enlighten Editors: Update this record