Institute Seminar - Positioning for Division: Spatial Logic of Mitotic Kinase Regulation

Precise regulation of kinase signaling is essential for ensuring mitotic progression and cell cycle fidelity. Decades of research have illuminated how mitotic kinases orchestrate the dynamic architecture and function of key cellular structures such as spindles and kinetochores. Despite these advances, critical aspects of mitotic kinase regulation remain poorly understood. This presentation will explore two independent lines of investigation that address underexplored facets of mitotic kinase signaling. The first part will highlight our recent work examining the roles of tyrosine kinase signaling during mitosis. Using an innovative phosphotyrosine enrichment strategy based on an engineered SH2 "superbinder" domain with enhanced affinity for phosphotyrosine-containing peptides, global pTyr dynamics were quantitatively profiled throughout the cell cycle. This analysis revealed nearly 2,000 mitosis-specific phosphorylation events, representing, to our knowledge, the first comprehensive characterization of tyrosine phosphorylation dynamics in mitosis. In the second half of the talk, I will focus on our recent work elucidating the mechanisms governing MPS1 kinase localization to kinetochores. Our findings indicate demonstrate how autophosphorylation modulates MPS1 interaction with the NDC80 complex, revealing distinct binding modes that support preferential kinetochore association of the inactive kinase relative to its active form. Together, these studies expand current understanding of mitotic kinase regulation and point to novel layers of control over spatial and temporal kinase activity during cell division.