Characterization Of Plasmodium Falciparum Atypical Kinase Pfpk7 - Dependent Phosphoproteome

Keywords

intraerythrocytic cycle; isobaric tags; kinase-substrate pairs; malaria; PfPK7; phosphoproteomics; phosphorylation; Plasmodium falciparum; TMT

Abstract

PfPK7 is an "orphan" kinase displaying regions of homology to multiple protein kinase families. PfPK7 functions in regulating parasite proliferation/development as evident from the phenotype analysis of knockout parasites. Despite this regulatory role, the functions of PfPK7 in signaling pathways are not known. To better understand PfPK7-regulated phosphorylation events, we performed isobaric tag-based quantitative comparative phosphoproteomics of the schizont and segmenter stages from wild-type and pfpk7 - parasite lines. This analysis identified 3,875 phosphorylation sites on 1,047 proteins. Among these phosphorylation events, 146 proteins with 239 phosphorylation sites displayed reduction in phosphorylation in the absence of PfPK7. Further analysis of the phosphopeptides revealed three motifs whose phosphorylation was down regulated in the pfpk7 - cell line in both schizonts and segmenters. Decreased phosphorylation following loss of PfPK7 indicates that these proteins may function as direct substrates of PfPK7. We demonstrated that PfPK7 is active toward three of these potential novel substrates; however, PfPK7 did not phosphorylate many of the other proteins, suggesting that decreased phosphorylation in these proteins is an indirect effect. Our phosphoproteomics analysis is the first study to identify direct substrates of PfPK7 and reveals potential downstream or compensatory signaling pathways.

Publication Date

6-1-2018

Publication Title

Journal of Proteome Research

Volume

17

Issue

6

Number of Pages

2112-2123

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/acs.jproteome.8b00062

Socpus ID

85046469910 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85046469910

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