The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism

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Abstract
Dictyostelium discoideum is a widely studied model organism with both unicellular and multicellular forms in its developmental cycle. The Dictyostelium genome encodes 285 predicted protein kinases, similar to the count of the much more advanced Drosophila. It contains members of most kinase classes shared by fungi and metazoans, as well as many previously thought to be metazoan specific, indicating that they have been secondarily lost from the fungal lineage. This includes the entire tyrosine kinase–like (TKL) group, which is expanded in Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies not present in yeast or metazoa, suggesting that protein kinases have played key roles in the adaptation of Dictyostelium to its habitat. This study offers insights into kinase evolution and provides a focus for signaling analysis in this system. Protein kinases are eukaryotic enzymes involved in cell communication pathways, and transmit information from outside the cell or between subcellular components within the cell. About 2.5% of genes code for protein kinases, and mutations in many of these cause human disease. The authors characterize the complete set of protein kinases (kinome) from Dictyostelium discoideum, a social amoeba that responds to starvation by forming aggregates of cells, which then differentiate into multicellular fruiting bodies. Dictyostelium branched from the vertebrate lineage after plants but before fungi, and thus illuminates an interesting period in evolutionary history. By comparing the Dictyostelium kinome to those of other organisms, the authors find 46 types of kinases that appear to be conserved in all organisms, and are likely to be involved in fundamental cellular processes. Dictyostelium is an established model organism for studying many aspects of cell biology that are conserved in humans, and this exposition of conserved kinases will help to guide future studies. The Dictyostelium kinome also contains an impressive degree of creativity—almost half of the kinases are unique to Dictyostelium. Many of these Dictyostelium-specific kinases may be related to this organism's distinctive mechanism for coping with starvation.

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