LmxMPK4, a mitogen-activated protein (MAP) kinase homologue essential for promastigotes and amastigotes of Leishmania mexicana

Qiong Wang, Inga M Melzer, Martin Kruse, Claudia Sander-Juelch, Martin Wiese

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Conclusion: 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.

Original languageEnglish
Article number6
Number of pages9
JournalKinetoplastid Biology and Disease
Volume4
DOIs
Publication statusPublished - 29 Dec 2005

Keywords

  • Leishmania parasites
  • protein kinases
  • extracellular flagellated promastigotes
  • intracellular "non-flagellated" amastigotes
  • enzymes
  • LmxMPK4
  • mitogen-activated protein
  • MAP
  • drug target

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