M-phase MELK activity is regulated by MPF and MAPK

Caroline Badouel, Roman Körner, Marie Frank-Vaillant, Anne Couturier, Erich A. Nigg and Jean-Pierre TassanThe protein kinase MELK is implicated in the control of cell proliferation, cell cycleand mRNA splicing. We previously showed that MELK activity is correlated with itsphosphorylation level, is cell cycle dependent, and maximal during mitosis. Here we report onthe identification of T414, T449, T451, T481 and S498 as residues phosphorylated inXenopus MELK (xMELK) in M-phase egg extract. Phosphorylations of T449, T451, T481are specifically detected during mitosis. Results obtained in vivo showed that MPF andMAPK pathways are involved in xMELK phosphorylation. In vitro, MPF and MAPK directlyphosphorylate xMELK and MPF phosphorylates xMELK on T481. In addition,phosphorylation by MPF and MAPK enhances MELK activity in vitro. Taken together ourresults indicate that MELK phosphorylation by MPF and MAPK enhance its activity duringM-phase.