ArticleGenome biology2011
The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology.
Article in Genome biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71 citing papers in PubMed, 145 citations in OpenAlex.
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- Identification of target genes regulated by encystation-induced transcription factor Myb2 using knockout mutagenesis in Giardia lamblia.Parasites & vectors · 2022Article
- Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy.Antimicrobial agents and chemotherapy · 2022Article
- Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation.Signal transduction and targeted therapy · 2022Article
- Computational tools and resources for pseudokinase research.Methods in enzymology · 2022Review
- In vitro selection of Giardia duodenalis for Albendazole resistance identifies a β-tubulin mutation at amino acid E198K.International journal for parasitology. Drugs and drug resistance · 2021Article
- Retortamonads from vertebrate hosts share features of anaerobic metabolism and pre-adaptations to parasitism with diplomonads.Parasitology international · 2021Article
- A polo-like kinase modulates cytokinesis and flagella biogenesis in Giardia lamblia.Parasites & vectors · 2021Article
- Eukaryote-Conserved Methylarginine Is Absent in Diplomonads and Functionally Compensated in Giardia.Molecular biology and evolution · 2020Article
- Disc-associated proteins mediate the unusual hyperstability of the ventral disc inJournal of cell science · 2020Article
- The compact genome ofMicrobial genomics · 2020Article
- Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes.Developmental cell · 2020Review
- Nek8445, a protein kinase required for microtubule regulation and cytokinesis inMolecular biology of the cell · 2020Article
11 more citing papers are in PubMed but not listed here.
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8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe major human intestinal pathogen Giardia lamblia is a very early branching eukaryote with a minimal genome of broad evolutionary and biological interest.
resultsTo explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.
conclusionsThe reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.
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