An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei

The sleeping sickness parasite,Trypanosoma brucei, uses quorum sensing (QS) to balance proliferation and transmission potential in the mammal bloodstream. A signal transduction cascade regulates this process, a component of which is a divergent member of the DYRK family of protein kinases, TbDYRK. Phylogenetic and mutational analysis in combination with activity and phenotypic assays revealed that TbDYRK exhibits a pre-activated confirmation and an atypical HxY activation loop motif, unlike DYRK kinases in other eukaryotes. Phosphoproteomic comparison of TbDYRK null mutants with wild type parasites identified molecules that operate on both the inhibitory 'slender retainer' and activatory 'stumpy inducer' arms of the QS control pathway. One of these molecules, the RNA-regulator TbZC3H20, regulates parasite QS, this being dependent on the integrity of its TbDYRK phosphorylation site. This analysis reveals fundamental differences to conventional DYRK family regulation and links trypanosome environmental sensing, signal transduction and developmental gene expression in a coherent pathway.
Source: eLife - Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research

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Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
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Source: Cell Host and Microbe - Category: Microbiology Authors: Tags: Cell Host Microbe Source Type: research
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Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research
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Source: G3: Genes Genomes Genetics - Category: Genetics & Stem Cells Authors: Tags: Investigations Source Type: research
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Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
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Source: International Journal for Parasitology - Category: Parasitology Authors: Tags: Int J Parasitol Source Type: research
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Source: Tetrahedron - Category: Chemistry Authors: Tags: Tetrahedron Source Type: research
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Source: Biomedical Beat Blog - National Institute of General Medical Sciences - Category: Research Authors: Tags: Genes Cellular Processes Chromosomes Source Type: blogs
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