LmxMPK4, a mitogen-activated protein (MAP) kinase homologue essential for promastigotes and amastigotes of Leishmania mexicana.
BACKGROUND
Leishmania parasites undergo profound morphological and biochemical changes while passing through their life cycle. Protein kinases have been shown to be involved in the differentiation from the extracellular flagellated promastigotes to the intracellular "non-flagellated" amastigotes and vice versa. Moreover, these enzymes are likely involved in the regulation of the proliferation of the different life stages.


RESULTS
Here, we characterize LmxMPK4, a mitogen-activated protein (MAP) kinase homologue from Leishmania mexicana. The kinase reveals all sequence motifs for classification as a MAP kinase. LmxMPK4 proved to be active as a recombinant protein. The kinase is expressed in promastigotes and amastigotes. It was impossible to generate homozygous gene deletion mutants for LmxMPK4 in promastigotes. Moreover, amastigotes bearing only an episomal copy of the gene stably retained LmxMPK4 over a prolonged period without antibiotic pressure in infected mice.


CONCLUSIONS
LmxMPK4 is essential for promastigotes and amastigotes of Leishmania. It shows significant amino acid sequence divergence to mammalian MAP kinases. Thus, LmxMPK4 is a promising new drug target.
Wang
Qiong
Q
Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.
Melzer
Inga M
IM
Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.
Kruse
Martin
M
Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.
Sander-Juelch
Claudia
C
Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.
Wiese
Martin
M
Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard-Nocht-Strasse 74, D-20359 Hamburg, Germany.