title: Pfnek3: an atypical activator of a MAP kinase in Plasmodium falciparum.
abstract: The canonical mitogen-activated protein kinase (MAPK) signal cascade was previously suggested to be atypical in the malaria parasite. This raises queries on the existence of alternative mediators of plasmodial MAPK pathways. This study describes, Pfnek3, a malarial protein kinase belonging to the NIMA (Never in Mitosis, Aspergillus) family. Endogenous Pfnek3 is expressed during late asexual to gametocyte stages and lacks some classical protein kinase sequence motifs. Moreover, Pfnek3 is phylogenetically distant from mammalian NIMA-kinases. Recombinant Pfnek3 was able to phosphorylate and stimulate a malarial MAPK (Pfmap2). Contrastingly, this was not observed with two other kinases, Pfmap1 and human MAPK1, suggesting that the Pfnek3-Pfmap2 interaction may be specific for Pfmap2 regulation. In summary, our data reveal a malarial NIMA-kinase with the potential to regulate a MAPK. Possessing biochemical properties divergent from classical mammalian NIMA-kinases, Pfnek3 could potentially be an attractive target for parasite-selective anti-malarials.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, MD4A, 5 Science Drive 2, Singapore 117597, Republic of Singapore.
authors.forename: Yu Min
authors.initials: YM
authors.lastname: Lye
authors.forename: Maurice
authors.initials: M
authors.lastname: Chan
authors.forename: Tiow-Suan
authors.initials: TS
authors.lastname: Sim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D015800:Protozoan Proteins; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases