title: A novel FIKK kinase regulates the development of mosquito and liver stages of the malaria.
abstract: Protein phosphorylation is the most important post-translational event in the regulation of various essential signaling pathways in a cell. Here, we show the functional characterization of a FIKK family protein kinase of the rodent malaria parasite (PbMLFK), which is expressed only in mosquito and liver stages and contains two functional C-terminal PEXEL motifs. We demonstrate that this protein plays a role in mosquito and liver stages of parasite growth. The oocysts of PbMLFK-deficient parasites produced 4-fold fewer sporozoites. In the liver of infected mice, PbMLFK-deficient parasites grew 100-fold less than did wild type parasites. We also show that the C-terminal domain of this protein has a functional serine-threonine kinase and that its activity was inhibited by a known PKA inhibitor. Transcriptome analysis of infected host cells suggests that in absence of this protein expression of the 288 host mRNAs are perturbed which are primarily associated with the immune system, cell cycle and metabolism.
authors.affiliation: Infectious Diseases Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Dabbu Kumar
authors.initials: DK
authors.lastname: Jaijyan
authors.affiliation: Plant Immunity Laboratory, National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Verma
authors.affiliation: Infectious Diseases Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Agam Prasad
authors.initials: AP
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000502:physiology; D010962:Plasmodium berghei / Q000254:growth & development*; D010963:Plasmodium falciparum / Q000254:growth & development*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D034101:Sporozoites / Q000254:growth & development*
chemical_list: D017346:Protein Serine-Threonine Kinases