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

Détails

ID Serval
serval:BIB_8189F030C13D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum.
Périodique
Nature Communications
Auteur(s)
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., Doerig C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
11/2011
Volume
2
Pages
565
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
Animals, Humans, Malaria, Falciparum/metabolism, Phosphorylation, Plasmodium falciparum/metabolism, Plasmodium falciparum/pathogenicity, Proteomics/methods, Protozoan Proteins/metabolism
Pubmed
Open Access
Oui
Création de la notice
15/01/2014 13:34
Dernière modification de la notice
20/01/2021 7:26
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