Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage of Plasmodium falciparum Asexual Maturation.

Farah Aida Dahalan,Nurul Aiezzah Zakaria,Mohammed Noor Embi,Noraishah Mydin Abdul-Aziz,Lim Fei Tieng,Mogana Das Murtey,Jamaiah Ibrahim,Hasidah Mohd Sidek

doi:10.1155/2016/1645097

Abstract

Plasmodium falciparum mitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that the P. falciparum specific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages of P. falciparum and is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites' developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.

Highlights

The spread of antimalarial resistance, in Plasmodium falciparum populations, is an important factor in our inability to effectively control this deadly cause of malaria
Our studies showed that is PfMAP2 expressed in all stages of asexual Plasmodium development (Figure 1), it is expressed in the nucleus irrespective of MAPK activation suggesting a more profound role being played by PfMAP2 in contrast to PfMAP1
The amount of PfMAP2 protein is lowest compared to the rest, its phosphorylated intensity value is highest at 16.69% more than the nonphosphorylated PfMAP2

Summary

Introduction

The spread of antimalarial resistance, in Plasmodium falciparum populations, is an important factor in our inability to effectively control this deadly cause of malaria. MAP kinases have a potential role in the regulation of cell cycle machinery of the malaria parasite upstream of the signal transduction pathways involved in the control of Plasmodium falciparum proliferation. Further studies confirmed that PfMAP2 is expressed in both stages, sexual and asexual Both MAP kinases differ from a normal 3-cascade MAPK usually found in eukaryotes (MAPKKK-MAPKK-MAPK). PfMAP2 is unique in that it cannot be confined to a specific MAPK family Both enzymes were originally grouped within the extracellular signal-regulated kinase 1, ERK1/ERK2 family of MAP kinases, a comprehensive phylogenetic analysis [4] of the entire complement of human protein kinase sequences indicates that PfMAP1 is clearly closer to the recently described ERK7/8 [8, 9]. This study was carried out to comprehend and enhance the understanding of PfMAP2 protein in order to convey it as a potential drug target

Material and Methods

Results and Discussion

Conclusion