Identification and characterization of novel kinase, AKB14-3-3-1, which is a possible target of sleeping sickness.

点击翻译按钮获取中文摘要

Proteomics approach of searching Tb14-3-3 binding proteins identified a novel associated kinase of Tb14-3-3 (AKB1). Tb14-3-3 directly and specifically binds to AKB1 utilizing an amphipathic groove structure of Tb14-3-3. Critical amino acid motif forAKB1 substrate recognition was identified and in vivo AKB1 kinase activity was successfully monitored with phosphorylated substrate-specific antibody. Majority of AKB1 is associated with cytoskeleton and most of AKB1 substrates are also identified in the detergent-insoluble fraction of cell lysate. AKB1 knockdown or overexpression of wild type AKB1 but not kinase-dead AKB1, deregulated cytokinesis and cell division, suggesting that kinase activity of AKB1 is crucial for growth. The results from this study suggest that AKB1 associated with Tb14-3-3 modulates cytokinesis and cell cycle progression in Trypanosoma brucei by phosphorylating cytoskeleton-associated proteins.