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


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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    ABSTRACT: Maternal embryonic leucine zipper kinase (MELK) functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis. In these cellular processes, MELK functions by binding to numerous proteins. In general, the effects of multiple protein interactions with MELK are oncogenic in nature, and the overexpression of MELK in kinds of cancer provides some evidence that it may be involved in tumorigenic process. In this review, our current knowledge of MELK function and recent discoveries in MELK signaling pathway were discussed. The regulation of MELK in cancers and its potential as a therapeutic target were also described.
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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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    ABSTRACT: Maternal Embryonic Leucine zipper Kinase (MELK) was recently shown to be involved in cell division of Xenopus embryo epithelial cells. The cytokinetic furrow of these cells ingresses asymmetrically and is developmentally regulated. Two subpopulations of xMELK, the mMELK (for "mitotic" xMELK) and iMELK ("interphase" xMELK), which differ in their spatial and temporal regulation, are detected in Xenopus embryo. How cells regulate these two xMELK populations is unknown. In this study we show that, in epithelial cells, xMELK is present at a higher concentration at the apical junctional complex, in contrast to mesenchyme-like cells, which have uniform distribution of cortical MELK. Interestingly, mMELK and iMELK also differ by their requirements towards cell-cell contacts to establish their proper cortical localization both in epithelial and mesenchyme-like cells. Receptor for Activated protein Kinase C (RACK1), which we identified as an xMELK partner, co-localizes with xMELK at the tight junction. Moreover, a truncated RACK1 construct interferes with iMELK localization at cell-cell contacts. Collectively, our results suggest that iMELK and RACK1 are present in the same complex and that RACK1 is involved in the specific recruitment of iMELK at the apical junctional complex in epithelial cells of Xenopus embryos.
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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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    ABSTRACT: MELK is a serine/threonine kinase involved in several cell processes, including the cell cycle, proliferation, apoptosis and mRNA processing. However, its function remains elusive. Here, we explored its role in the Xenopus early embryo and show by knockdown that xMELK (Xenopus MELK) is necessary for completion of cell division. Consistent with a role in cell division, endogenous xMELK accumulates at the equatorial cortex of anaphase blastomeres. Its relocalization is highly dynamic and correlates with a conformational rearrangement in xMELK. Overexpression of xMELK leads to failure of cytokinesis and impairs accumulation at the division furrow of activated RhoA - a pivotal regulator of cytokinesis. Furthermore, endogenous xMELK associates and colocalizes with the cytokinesis organizer anillin. Unexpectedly, our study reveals a transition in the mode of cytokinesis correlated to cell size and that implicates xMELK. Collectively, our findings disclose the importance of xMELK in cytokinesis during early development and show that the mechanism of cytokinesis changes during Xenopus early development.
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