title: Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum.
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.
authors: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK.
authors: Lev
authors: L
authors: Solyakov
authors: Jean
authors: J
authors: Halbert
authors: Mahmood M
authors: MM
authors: Alam
authors: Jean-Philippe
authors: JP
authors: Semblat
authors: Dominique
authors: D
authors: Dorin-Semblat
authors: Luc
authors: L
authors: Reininger
authors: Andrew R
authors: AR
authors: Bottrill
authors: Sharad
authors: S
authors: Mistry
authors: Abdirhaman
authors: A
authors: Abdi
authors: Clare
authors: C
authors: Fennell
authors: Zoe
authors: Z
authors: Holland
authors: Claudia
authors: C
authors: Demarta
authors: Yvan
authors: Y
authors: Bouza
authors: Audrey
authors: A
authors: Sicard
authors: Marie-Paule
authors: MP
authors: Nivez
authors: Sylvain
authors: S
authors: Eschenlauer
authors: Tenzing
authors: T
authors: Lama
authors: Divya Catherine
authors: DC
authors: Thomas
authors: Pushkar
authors: P
authors: Sharma
authors: Shruti
authors: S
authors: Agarwal
authors: Selina
authors: S
authors: Kern
authors: Gabriele
authors: G
authors: Pradel
authors: Michele
authors: M
authors: Graciotti
authors: Andrew B
authors: AB
authors: Tobin
authors: Christian
authors: C
authors: Doerig
mesh_terms: D000818:Animals; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity*; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins