Mos activates MAP kinase in mouse oocytes through two opposite pathways

Verlhac, Marie‐Hélène; Lefebvre, Christophe; Kubiak, Jacek Z.; Umbhauer, Muriel; Rassinier, Pascale; Colledge, William H.; Maro, Bernard

doi:10.1093/emboj/19.22.6065

Cited by 91 publications

(91 citation statements)

References 55 publications

(92 reference statements)

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“…Another potential explanation could relate to ERK desensitization. ERK phosphorylation is negatively regulated by various phosphatases (Lu et al, 2002;Verlhac et al, 2000) and indeed, our present studies indicate that EphA2 stimulation of ERK kinases is quite transient. Moreover, we have found that EphA2 stimulation of ERK activity in PC-3 cells occurs more rapidly and more transiently than in any of the other cell systems that we have investigated (data not shown).…”

Section: Discussionsupporting

confidence: 67%

Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade

2002

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Intracellular signaling by receptor tyrosine kinases regulates many different aspects of cell behavior. Recent studies in our laboratory and others have demonstrated that the EphA2 receptor tyrosine kinase critically regulates tumor cell growth, migration and invasiveness. Although the cellular consequences of EphA2 signaling have been the focus of recent attention, the biochemical changes that are triggered by ligand-mediated activation of EphA2 remain largely unknown. Herein, we demonstrate that ligand stimulation of EphA2 promotes the nucleus translocation and phosphorylation of ERK kinases, followed by an increase in nuclear induction of the Elk-1 transcription factor. Ligand-mediated activation allows EphA2 to form a molecular complex with the SHC and GRB2 adaptor proteins. Specifically, we demonstrate that tyrosine phosphorylated EphA2 interacts with the PTB and SH2 domains of SHC. We also show that the interaction of EphA2 with GRB2 is indirect and mediated by SHC and that this complex is necessary for EphA2-mediated activation of ERK kinases. These studies provide a novel mechanism to demonstrate how EphA2 can convey information from the cell exterior to the nucleus.

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Section: Discussionsupporting

confidence: 67%

Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade

2002

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“…As well, some studies [8,13] did not include cases with large polar body into consideration. A large 1 PB would indicate a problem with check point genes and mitogen activated protein Kinase, cMOS and involving first meiotic spindle establishment [19]. In addition, few of these studies included only "good quality" infertile women [11,13] while others defined poor responders as those having below 10 oocytes per retrieval [8].…”

Section: Discussionmentioning

confidence: 99%

Does first polar body morphology predict oocyte performance during ICSI treatment?

Younis

Radin

Izhaki

et al. 2009

J Assist Reprod Genet

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Purpose To gain insight into the morphology of the first polar body (1 PB) in ICSI patients and to explore whether it could predict mature oocyte viability and performance in this setting. Methods Seventy two consecutive women planned to perform ICSI treatment were prospectively recruited for this study. All oocytes retrieved underwent evaluation for nuclear maturity and accurate assessment of 1 PB morphology. MII oocytes were cultured in separate groups in each woman in accordance with two different categories of 1 PB morphology. Category A included normal intact round or ovoid 1 PB and category B included abnormal fragmented 1 PB. Each oocyte was followed throughout fertilization, embryo cleavage and embryo transfer. Cycles that reached embryo transfer, were divided into three groups in accordance with 1 PB morphology. Group I included only category A 1 PB embryos, group II included categories A and B 1 PB embryos, whereas group III included only category B 1 PB embryos. Results A total of 687 oocytes were aspirated and 553 MII oocytes underwent ICSI leading to 410 zygotes showing normal fertilization on day one. Three hundred ninety seven embryos cleaved on day two and a total of 176 embryos were replaced into the uterus. Clinical implantation and pregnancy rates were significantly correlated with the morphology of the 1 PB corresponding to 31%, 9% and 2% and 61%, 24% and 5%, in groups I, II and III respectively. Conclusions Our findings demonstrate that 1 PB morphology is related to mature oocyte viability and it has the potential to predict oocyte performance and pregnancy achievement in infertile women undergoing ICSI treatment.

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“…Verlhac et al [35] showed that MOS activated MAP kinase through two opposite pathways: activation of MEK and inhibition of protein phosphatase. We and others found that inhibition of protein phosphatase by okadaic acid (OA) induced precocious MAP kinase activation in mouse and pig oocytes [36,37]. OA treatment of fertilized mouse or pig eggs resulted in prompt phosphorylation of MAP kinase, disassembly of microtubules around the pronuclear area, chromatin condensation, and nuclear membrane breakdown [38,39].…”

Section: Discussionmentioning

confidence: 99%

Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest

et al. 2003

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In this study we used U0126, a potent and specific inhibitor of MEK, to study the roles of MEK/ERK/p90 rsk signaling pathway in the meiotic cell cycle of mouse oocytes. The phosphorylation of MAP kinase and p90 rsk in the oocytes treated with 1.5 M U0126 was the same as that in oocytes cultured in drug-free medium. With 1.5 M U0126 treatment, the spindles appeared normal as they formed in oocytes, but failed to maintain its structure. Instead, the spindle lost one pole or elongated extraordinarily. After further culture, some oocytes extruded gigantic polar bodies (>30 m) that later divided into two small ones. Some oocytes underwent symmetric division and produced two equal-size daughter cells in which normal spindles formed. In oocytes with different division patterns, MAP kinase was normally phosphorylated. When the concentration of U0126 was increased to 15 M, the phosphorylation of both MAPK and p90 rsk were inhibited, while symmetric division was decreased. When incubating in medium containing 15 M U0126 for 14 h, oocytes were activated, but part of them failed to emit polar bodies. MII oocytes were also activated by 15 M U0126, at the same time the dephosphorylation of MAP kinase and p90 rsk was observed. Our results indicate that 1) MEK plays important but not indispensable roles in microtubule organization; 2) MEK keeps normal meiotic spindle morphology, targets peripheral spindle positioning and regulates asymmetric division by activating some unknown substrates other than MAP kinase /p90 rsk ; and 3) activation of MEK/ERK/p90 rsk cascade maintains MII arrest in mouse oocytes.

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Mos activates MAP kinase in mouse oocytes through two opposite pathways

Cited by 91 publications

References 55 publications

Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade

Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade

Does first polar body morphology predict oocyte performance during ICSI treatment?

Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest

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