Phosphoregulation of human Mps1 kinase

Rebecca K Tyler , Matthew L H Chu , Hannah Johnson , Edward A Mckenzie , Simon J Gaskell , Patrick A Eyers (1)

1 Faculty of Life Sciences [Manchester]

The dual-specificity protein kinase Mps1 is a phosphoprotein required for error-free mitotic progression in eukaryotes. In this study, we have investigated human Mps1 phosphorylation using combined mass spectrometric, mutational and phosphospecific antibody approaches. We identify sixteen sites of Mps1 autophosphorylation in vitro, several of which are required for catalytic activity after expression in bacteria or in cultured human cells. Using novel phosphospecific antibodies, we show that endogenous Mps1 is phosphorylated on Thr686 and Ser821 during mitosis, and demonstrate that phosphorylated Mps1 localises to the centrosomes of metaphase cells. Taken together, these data reveal the complexity of Mps1 regulation by multi-site phosphorylation, and demonstrate conclusively that phosphorylated Mps1 associates with centrosomes in mitotic human cells.

Mots clés: Life Sciences

Rebecca K Tyler, Matthew L H Chu, Hannah Johnson, Edward A Mckenzie, Simon J Gaskell, et al.. Phosphoregulation of human Mps1 kinase. Biochemical Journal, 2008, 417 (1), pp.173-181. ⟨10.1042/BJ20081310⟩. ⟨hal-00479059⟩