Roles and Regulation of CK1 Protein Kinases
In S. pombe, formation and constriction of the cytokinetic ring requires a protein kinase signaling pathway called the septation initiation network (SIN) that is scaffolded at the spindle pole body (SPB; i.e. yeast equivalent of the centrosome) (Morrell et al., 2004; Rosenberg et al., 2006). We discovered that members of the highly conserved CK1 protein kinase family (Hhp1 and Hhp2) inhibit SIN activity during a mitotic checkpoint arrest to prevent cytokinesis when chromosomes have not segregated (Johnson et al., 2013). Because CK1 protein kinases contribute to multiple biological processes, we went on to study how they are tailored to function in compartmentalized signaling events such as at the SPB. We found that their catalytic domains but not their enzymatic function are used for SPB targeting and that this targeting strategy is conserved in human CK1δ/ε localization to centrosomes (Elmore et al., 2018).
Our results further piqued our interest in CK1 enzymes and we went on to identify interacting partners of CK1δ and CK1ε (Guillen et al., 2020) and their substrates (manuscript in preparation) in human cells. And, we are continuing to explore the implications of these interactions.
Our studies of CK1 enzymes in yeast and mammalian cells have raised many new questions about these poorly understood protein kinases. What controls their enzymatic activity? How do they get to spindle poles and what are they doing there? How do they contribute to human disease? We are addressing these questions with phosphoproteomic approaches as well as biochemical and genetic studies in yeast and human cells. If you’re interested in studying these fascinating protein kinases Join Us.