What is the primary role of the Mps1 kinase?
Spindle assembly checkpoint activation hinges on kinase Mps1, also known as TTK, a dual specificity protein kinase recruited to unattached kinetochores. In prometaphase, Mps1 binds Ndc80 complex through competition with microtubules, positioning it near scaffold KNL1. Mps1 phosphorylates multiple MELT repeats on KNL1 at conserved methionine-glutamate-leucine-threonine motifs, converting them into phospho-docking sites for Bub3-Bub1 and Bub3-BubR1 complexes. Additionally, Mps1 phosphorylates Mad1 at C-terminus facilitating catalytic conversion of open O-Mad2 to closed C-Mad2, the conformer capa
Ref: London & Biggins, Mps1 Dependent KNL1 MELT Phosphorylation, Genes Dev 2014; Alberts et al., Chapter 17, SAC Kinase Cascade.