title: Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage of Plasmodium falciparum Asexual Maturation.
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.
authors.affiliation: School of Biosciences & Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
authors.forename: Farah Aida
authors.initials: FA
authors.lastname: Dahalan
authors.affiliation: School of Biosciences & Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
authors.forename: Hasidah Mohd
authors.initials: HM
authors.lastname: Sidek
authors.affiliation: Cluster of Integrative Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia.
authors.forename: Mogana Das
authors.initials: MD
authors.lastname: Murtey
authors.affiliation: School of Biosciences & Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
authors.forename: Mohammed Noor
authors.initials: MN
authors.lastname: Embi
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Jamaiah
authors.initials: J
authors.lastname: Ibrahim
authors.affiliation: Faculty of Pharmacy, University of Technology MARA, 42300 Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Lim
authors.initials: L
authors.lastname: Fei Tieng
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Nurul Aiezzah
authors.initials: NA
authors.lastname: Zakaria
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Noraishah Mydin
authors.identifier: 0000-0002-2447-3211
authors.initials: NM
authors.lastname: Abdul-Aziz
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000962:Antimalarials / Q000627:therapeutic use; D002467:Cell Nucleus / Q000201:enzymology*; D019295:Computational Biology; D004912:Erythrocytes / Q000469:parasitology; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020935:MAP Kinase Signaling System; D016778:Malaria, Falciparum / Q000188:drug therapy; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D010766:Phosphorylation; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000201:enzymology*; D015800:Protozoan Proteins / Q000502:physiology; D011817:Rabbits; D013379:Substrate Specificity; D053058:Trophozoites / Q000201:enzymology
chemical_list: D000906:Antibodies; D000962:Antimalarials; D015800:Protozoan Proteins