Article

M-phase MELK activity is regulated by MPF and MAPK

CNRS UMR 6061 Génétique et Développement, Université de Rennes, Rennes, France.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 05/2006; 5(8):883-9.
Source: PubMed

ABSTRACT

The protein kinase MELK is implicated in the control of cell proliferation, cell cycle and mRNA splicing. We previously showed that MELK activity is correlated with its phosphorylation level, is cell cycle dependent, and maximal during mitosis. Here we report on the identification of T414, T449, T451, T481 and S498 as residues phosphorylated in Xenopus MELK (xMELK) in M-phase egg extract. Phosphorylations of T449, T451, T481 are specifically detected during mitosis. Results obtained in vivo showed that MPF and MAPK pathways are involved in xMELK phosphorylation. In vitro, MPF and MAPK directly phosphorylate xMELK and MPF phosphorylates xMELK on T481. In addition, phosphorylation by MPF and MAPK enhances MELK activity in vitro. Taken together our results indicate that MELK phosphorylation by MPF and MAPK enhance its activity during M-phase.

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Available from: Caroline Badouel, Dec 11, 2014
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    • "MPF and MAPK directly phosphorylate xMELK and enhance its kinase activity in vitro. In addition, the specific phosphorylation of threonine 449, threonine 451, and threonine 481 in M phase is detected during Xenopus oocyte maturation in embryos and in Xenopus cultured cells[55]. Thus, many of these interactions result in aberrant signaling involved in cell cycle progression, TGF-β signaling, embryonic development, ASK1-mediated signaling, and apoptosis. Some of these interactions are often ambiguous, and the function of MELK is only partially clear. "
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    • "In human cells and Xenopus embryos, MELK is phosphorylated during mitosis, which correlates with the increase in its catalytic activity (Blot et al., 2002; Davezac et al., 2002). In xMELK, we have identified multiple sites phosphorylated specifically during mitosis (Badouel et al., 2006). The two major mitotic kinases, cyclin B-CDK1 complex and mitogen-activated protein kinase ERK2, participate in these phosphorylation events and enhance MELK activity in vitro. "
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    • "xMELK to -tubulin (used as a loading control) ratios are indicated. In MII oocytes, xMELK is phosphorylated and, consequently, its electrophoretic mobility is decreased compared with that of PI and embryos (Blot et al., 2002; Badouel et al., 2006). (B)Northern blot analysis with an xMELK probe of oocytes treated with 2 or 4 ng of AS Co, AS9, AS11 oligos or untreated (–). "
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