title: Global analysis of protein expression and phosphorylation of three stages of Plasmodium falciparum intraerythrocytic development.
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.
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida 32826, United States.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Pease
authors.forename: Edward L
authors.initials: EL
authors.lastname: Huttlin
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jedrychowski
authors.forename: Eric
authors.initials: E
authors.lastname: Talevich
authors.forename: John
authors.initials: J
authors.lastname: Harmon
authors.forename: Timothy
authors.initials: T
authors.lastname: Dillman
authors.forename: Natarajan
authors.initials: N
authors.lastname: Kannan
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
authors.forename: Ratna
authors.initials: R
authors.lastname: Chakrabarti
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Debopam
authors.initials: D
authors.lastname: Chakrabarti
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D011494:Protein Kinases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D013194:Staining and Labeling
chemical_list: D010750:Phosphoproteins; D020543:Proteome; D015800:Protozoan Proteins; D011494:Protein Kinases
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