ArticlePloS one2013
Identification of a secreted casein kinase 1 in Leishmania donovani: effect of protein over expression on parasite growth and virulence.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Characterization of the dual functions of Leishmania CK1.2 in both the parasite and the macrophage.PloS one · 2026Article
- Activity-based chemoproteomic profiling reveals the active kinome ofFrontiers in pharmacology · 2025Article
- Distinguishing functions of trypanosomatid protein kinases.Trends in parasitology · 2022Review
- Reporter gene systems: A powerful tool forCurrent research in microbial sciences · 2022Article
- Profilin is involved in G1 to S phase progression and mitotic spindle orientation during Leishmania donovani cell division cycle.PloS one · 2022Article
- Challenges and Tools for In VitroPathogens (Basel, Switzerland) · 2021Review
- Review
- Mapping immune variation andeLife · 2021Article
- Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.Nature communications · 2021Article
- Dangerous Duplicity: The Dual Functions of Casein Kinase 1 in Parasite Biology and Host Subversion.Frontiers in cellular and infection microbiology · 2021Review
- Review
- Evaluation of Different Concentrations of Imatinib on the Viability ofAdvanced biomedical research · 2019Article
- Development of NanoLuc-PEST expressing Leishmania mexicana as a new drug discovery tool for axenic- and intramacrophage-based assays.PLoS neglected tropical diseases · 2018Article
- Emerging therapeutic targets for treatment of leishmaniasis.Expert opinion on therapeutic targets · 2018Review
- Characterisation of Casein Kinase 1.1 inBioMed research international · 2017Article
- Article
- Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions.BMC genomics · 2015Article
- The genetics of Leishmania virulence.Medical microbiology and immunology · 2015Review
- Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1.PloS one · 2015Article
- Genetically modified organisms and visceral leishmaniasis.Frontiers in immunology · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Casein kinase 1 (CK1) plays an important role in eukaryotic signaling pathways, and their substrates include key regulatory proteins involved in cell differentiation, proliferation and chromosome segregation. The Leishmania genome encodes six potential CK1 isoforms, of which five have orthologs in other trypanosomatidae. Leishmania donovani CK1 isoform 4 (Ldck1.4, orthologous to LmjF27.1780) is unique to Leishmania and contains a putative secretion signal peptide. The full-length gene and three shorter constructs were cloned and expressed in E. coli as His-tag proteins. Only the full-length 62.3 kDa protein showed protein kinase activity indicating that the N-terminal and C-terminal domains are essential for protein activity. LdCK1.4-FLAG was stably over expressed in L. donovani, and shown by immunofluorescence to be localized primarily in the cytosol. Western blotting using anti-FLAG and anti-CK1.4 antibodies showed that this CK1 isoform is expressed and secreted by promastigotes. Over expression of LdCK1.4 had a significant effect on promastigote growth in culture with these parasites growing to higher cell densities than the control parasites (wild-type or Ld:luciferase, P<0.001). Analysis by flow cytometry showed a higher percentage, ∼4-5-fold, of virulent metacyclic promastigotes on day 3 among the LdCK1.4 parasites. Finally, parasites over expressing LdCK1.4 gave significantly higher infections of mouse peritoneal macrophages compared to wild-type parasites, 28.6% versus 6.3%, respectively (p = 0.0005). These results suggest that LdCK1.4 plays an important role in parasite survival and virulence. Further studies are needed to validate CK1.4 as a therapeutic target in Leishmania.
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