Global Analysis of Protein Expression and Phosphorylation of Three Stages of Plasmodium falciparum Intraerythrocytic Development

    Authors

    B. N. Pease; E. L. Huttlin; M. P. Jedrychowski; E. Talevich; J. Harmon; T. Dillman; N. Kannan; C. Doerig; R. Chakrabarti; S. P. Gygi;D. Chakrabarti

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    Abbreviated Journal Title

    J. Proteome Res.

    Keywords

    malaria; Plasmodium falciparum; intraerythrocytic cycle; proteomics; phosphoproteomics; isobaric tags; phosphorylation; phosphorylation; motifs; kinase-substrate pairs; MASS-SPECTROMETRY; LIFE-CYCLE; SACCHAROMYCES-CEREVISIAE; PHOSPHOPROTEOME; ANALYSIS; QUANTITATIVE PROTEOMICS; MALARIA PARASITES; KINASE; DATABASE; REVEALS; FAMILY; Biochemical Research Methods

    Abstract

    During asexual intraerythrocytic development, Plasmodium falciparum diverges from the paradigm of the eukaryotic cell cycles by undergoing multiple rounds of DNA replication and nuclear division without cytokinesis. A better understanding of the molecular switches that coordinate a myriad of events for the progression of the parasite through the intraerythrocytic developmental stages will be of fundamental importance for rational design of intervention strategies. To achieve this goal, we performed isobaric tag-based quantitative proteomics and phosphoproteomics analyses of three developmental stages in the Plasmodium asexual cycle and identified 2767 proteins, 1337 phosphoproteins, and 6293 phosphorylation sites. Approximately 34% of identified proteins and 75% of phosphorylation sites exhibit changes in abundance as the intraerythrocytic cycle progresses. Our study identified 43 distinct phosphorylation motifs and a range of potential MAPK/CDK substrates. Further analysis of phosphorylated kinases identified 30 protein kinases with 126 phosphorylation sites within the kinase domain or in N- or C-terminal tails. Many of these phosphorylations are likely CK2-mediated. We define the constitutive and regulated expression of the Plasmodium proteome during the intraerythrocytic developmental cycle, offering an insight into the dynamics of phosphorylation during asexual cycle progression. Our system-wide comprehensive analysis is a major step toward defining kinase-substrate pairs operative in various signaling networks in the parasite.

    Journal Title

    Journal of Proteome Research

    Volume

    12

    Issue/Number

    9

    Publication Date

    1-1-2013

    Document Type

    Article

    Language

    English

    First Page

    4028

    Last Page

    4045

    WOS Identifier

    WOS:000330147800019

    ISSN

    1535-3893

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