ArticleKinetoplastid biology and disease2005
LmxMPK4, a mitogen-activated protein (MAP) kinase homologue essential for promastigotes and amastigotes of Leishmania mexicana.
Article in Kinetoplastid biology and disease, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective.Frontiers in cellular and infection microbiology · 2023Review
- Promastigote-to-Amastigote Conversion inPathogens (Basel, Switzerland) · 2022Review
- Review
- Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.Nature communications · 2021Article
- Alkyl and Aryl Derivatives Based onMolecules (Basel, Switzerland) · 2020Article
- Review
- Article
- Genetically Validated Drug Targets in Leishmania: Current Knowledge and Future Prospects.ACS infectious diseases · 2018Review
- Conditional gene deletion with DiCre demonstrates an essential role for CRK3 in Leishmania mexicana cell cycle regulation.Molecular microbiology · 2016Article
- Kinases as druggable targets in trypanosomatid protozoan parasites.Chemical reviews · 2014Review
- Pharmacological assessment defines Leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection.Antimicrobial agents and chemotherapy · 2014Article
- Modulation of Leishmania major aquaglyceroporin activity by a mitogen-activated protein kinase.Molecular microbiology · 2012Article
- Downregulation of mitogen-activated protein kinase 1 of Leishmania donovani field isolates is associated with antimony resistance.Antimicrobial agents and chemotherapy · 2012Article
- Trypanosoma brucei: Two mitogen activated protein kinase kinases are dispensable for growth and virulence of the bloodstream form.Experimental parasitology · 2011Article
- Parasite mitogen-activated protein kinases as drug discovery targets to treat human protozoan pathogens.Journal of signal transduction · 2011Article
- Molecular cloning and characterization of mitogen-activated protein kinase 2 in Trypanosoma cruzi.Cell cycle (Georgetown, Tex.) · 2010Article
- Homology modeling and atomic level binding study of Leishmania MAPK with inhibitors.Journal of molecular modeling · 2010Article
- Leishmania major MPK7 protein kinase activity inhibits intracellular growth of the pathogenic amastigote stage.Eukaryotic cell · 2010Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundLeishmania 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.
resultsHere, 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.
conclusionLmxMPK4 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.
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