Mapk and oocyte activation

Bub1 is activated by the protein kinase p90rsk during. Morerecently, mitogen activated protein kinase mapk,whichis highly activated throughout oocyte maturation 812, has been identified as one of the major downstream targets of mos 17. An important feature of meiotic maturation is an extensive network of feedback signalling mostly downstream of mpf activation, which is responsible for the generation of an allornone response ensuring that the. Mapk was activated at g2m transition during meiosis. In oocytes, mapk is activated independently of growth factors and tyrosine. Elevated akt kinase activity is necessary for meiosis to resume because this enzyme regulates polar body emission and spindle organization. Activation of p38 mapk during porcine oocyte maturation. Cb1 cannabinoid receptor drives oocyte maturation and embryo. Other members of the mapk family that are involved in meiotic maturation of oocytes are the extracellular regulated kinases erks 11, such as erk1 and erk2, which are members of the. Phosphorylation of mitogen activated protein kinase is regulated by protein kinase c, cyclic 3,5adenosine. Roles of mapk and spindle assembly checkpoint in spontaneous. Mos activates map kinase in mouse oocytes through two.

As an important physical substrate of mapk, p 90 rsk mediates numerous mapk functions. Biochemically, oocyte maturation begins with a drop in camp levels, activation of aurora a, upregulation of mos translation and stability, activation of the mosmek mek1map kinase p42 mapk or erk2 cascade, and ultimately activation of cyclincdk1. Effect of single and combined treatments with mpf or mapk. In 1990, melanie cobb and her colleagues described the mammalian homolog for the mitogen activated protein kinase mapk found in yeast by demonstrating that insulin action induced phosphorylation of a catalytic activity that could phosphorylate microtubuleassociated protein 2 map2. Recently it has been demonstrated that endocannabinoid signaling governs sperm activation via the sex hormone progesterone 20, a nongenomic signal that is also required for oocyte maturation 21. Activation of mitogenactivated protein kinase mapk in maturing mouse oocytes occurs after synthesis of mos, a mapkkk. However, an assay for mapk activation in cells treated with submaximal progesterone concentrations reveals intermediate levels of mapk activation. Xenopus oocytes and eggs provide a dramatic example of how the consequences of p42 mitogen activated protein kinase p42 mapk activation depend on the particular context in which the activation occurs. A mapk cascade couples maternal mrna translation and. The functions of the mosmapk pathway in oocyte maturation differs between the mouse and xenopus 16.

Xenopusoocytes can also undergo gvbd in the absence of mapk activation, although with delayed kinetics. Although mpf activation and oocyte maturation can be obtained in vivo by microinjection of constitutively active forms of mapks gotoh et al. Leptin is a modulator of oocyte maturation and follicular development in swine. This study was designed to investigate the mechanism causing sa and miii arrest.

Apparently, testing this framework of thinking requires a different set of experiments, including characterization. The protooncogene csrc is involved in primordial follicle activation through the pi3k, pkc and mapk signaling pathways. Likewise, the dephosphorylation and inactivation of p42 mapk are critical for the progression of fertilized eggs out of meiosis and through the first mitotic cell cycle. The first evidence that links the endocannabinoid system and the oocyte matu. Mapk was transiently activated during mitosis in cycling xenopus egg extracts after activation of the cyclindependent kinase cdc2cyclin b. Other members of the mapk family that are involved in meiotic maturation of oocytes are the extracellular regulated kinases erks, such as erk1 and erk2, which are members of the canonical mapk family activated in response to various extracellular signaling molecules via an upstream small gprotein ras. Whereas few oocytes collected from sd rats at h after hcg injection that showed 100% of mitogenactivated protein. Xenopus mapk and mapkk are activated during progesteroneinduced oocyte maturation almost simultaneously with the activation of mpf18, 19, 20, 21. The present study investigated the phosphorylation pattern of mitogenactivated protein kinase mapk in cumulusoocyte complexes cocs during spontaneous and fshlhinduced in vitro maturation ivm. The present study was designed to investigate the expression and possible function of p38 mapk in porcine oocytes during maturation. Distinct, constitutively active mapk phosphatases function. During xenopus oocyte maturation, the mos protein kinase is synthesized and activates the map kinase cascade. Nucleus, cytoskeleton, and mitogenactivated protein.

The timing of activation of mapk during oocyte maturation, unlike mpf, varies in mammalian species and. Mapk activation has been reported to be essential in xenopus oocytes gvbd. Signalling pathways in oocyte meiotic maturation journal of. Microcystinlr influences the in vitro oocyte maturation of. In oocytes, the activation of mos, mek, and p42 mapk is required for progesteroneinduced cdc2 activation, and activated forms of any of these proteins can bring about cdc2 activation. A ligand called gurken red arrow that is localized in the underlying oocyte. Mapk activation during oocyte maturation was dependent mostly on mos, which is a mapk kinase kinase mapkkk and also the upstream activator of mapk dupre et al. Obox4silencingactivated stat3 and mpfmapk signaling. Toward modeling of a general mechanism of mpf formation. Sigma or, as a control group, with the same amount of saline after being primed with pmsg for 48 h. Thus, p42 mapk is an excellent candidate for one of the kinases involved in initiating cdc25 activation during xenopus oocyte maturation. The drosophila p38 mapk pathway is required during oogenesis. These include meiotic resumption, 2pb extrusion, pn formation and the initiation of the first mitotic cycle.

Involvement of mitogenactivated protein kinase cascade during. Methods for artificial oocyte activation aoa try to bypass fertilization failure by influencing physiological processes that. The other is a mitogenactivated protein kinase mapk pathway, which. If mapk activity in the oocytes is essential for gvb in this gonadotropindependent system in vitro, it is. The dynamics of mapk inactivation at fertilization in mouse eggs. Oocyte activation an overview sciencedirect topics. The mapk rsk pathway is also necessary for the activation of a histone h3 kinase, possibly aurora b, during oocyte maturation. We find that hsp90 function is required for activation and phosphorylation of mos and full activation of the map kinase cascade. Redundant pathways for cdc2 activation in xenopus oocyte. These findings establish an essential role of erk mapk in cdc25 activation during xenopus oocyte maturation and suggest potential roles of the erk mapk family in hcdc25c activation during somatic cell cycle.

We reported previously that an antimapkk neutralizing antibody inhibited progesterone or mos induced initiation of oocyte maturation. The objectives of the present paper were to study the involvement and possible interactions of both camppka and protein phosphatases in bufo arenarum oocyte maturation and to determine if these pathways are independent or not of the map kinase mapk cascade. Mitogenactivated protein kinase mapk and mapk kinase mapkk are activated during xenopus oocyte maturation concomitant with the activation of maturation promoting factor mpf. The contribution of oocyte and spermrelated causes of fertilization failure is discussed. Direct roles of the signaling kinase rsk2 in cdc25c. Participation of mapk, pka and pp2a in the regulation of.

If this twostep activation model is correct, mapk, cdc2, and rsk each may be able to both partially activate cdc25c and generate primed cdc25c for the secondary phosphorylation and full activation during xenopus oocyte maturation. Both processes require activation of mitogen activated protein kinase mapk in granulosa cells. Signalling pathways in oocyte meiotic maturation journal. Pi3kakt andor mapk signaling play a role in oocyte maturation. Meiotic mapk activity is controlled by the oocyte specific protein kinase, mos, which activates the mapk kinase, mek. Leptin and mitogenactivated protein kinase mapk in. In mammalian species, activation of mapk in cumulus cells is necessary for gonadotropininduced meiotic resumption of oocytes, while mapk. Changes in mpf and mapk activities in porcine oocytes. Mapkk and mapk can be activated downstream of mos, as injection of mos protein into oocytes or addition of mos protein into oocyte extracts rapidly activates mapkk and mapk 22, 23, 24. Sperm entry causes calcium release into the oocyte.

Mapk is activated by a cascade of protein kinase phosphorylation and plays pivotal roles in regulating meiosis process in oocytes. This is the first genetic demonstration of an essential function for a p38 mapk pathway in development. Regulation of cdc25c by erkmap kinases during the g2. Progesterone stimulation of xenopus oocytes sets off a signalling pathway culminating in the translation and stabilization of mos, an upstream activator of map kinase. A later decline in the activity of mitogenactivated protein kinase mapk then leads to the completion of activation which is marked by the formation of pronuclei.

In mammals, this has been proposed to be caused by the introduction of phospholipase c isoform zeta plc. Many studies on the physiology of fertilization in mammals have shown that oocyte activation is triggered by the sperm factor. Mitogenactivated protein kinase activity in cumulus cells is. Initiation of xenopus oocyte maturation by activation of the. Maturationpromoting factor mpf and mapk are normally inactive in gv stage oocytes but were activated prematurely in arrested gv stage oocytes by 3isobutyl1metylxanthine ibmx in vitro after obox4 rna interference rnai. Involvement of mitogenactivated protein kinase cascade. To investigate whether mos acts only through mek1, we microinjected constitutively active forms of mek1 mek1s218ds222d referred herein as mek and raf.

Pi3kakt and or mapk signaling play a role in oocyte maturation. Even when mos synthesis and mapk activation are inhibited, rana oocytes can mature in response to progesterone. Here evidence is presented that the allornone character of the response is generated by the mitogenactivated protein kinase mapk cascade. The following experiments were designed to determine the dynamics of mpf and mapk during oocyte sa to confirm that the spindle defects were caused by premature mapk inactivation and that the miii arrest was triggered by reactivation of mpf and mapk. But what happens to the egg, also called an oocyte. Mitogenactivated protein kinase activity in cumulus cells.

Studies in the last decade revealed that mapk cascade plays pivotal roles in regulating the meiotic cell cycle progression of oocytes. Roles of map kinase signaling pathway in oocyte meiosis. Mitogenactivated protein kinase phosphorylation patterns. Xenopus oocytes can also undergo gvbd in the absence of mapk activation, although with delayed kinetics. Mos has been implicatedin the activation andstabilization ofp34cdc2kinase as maturation promoting factor mpf 4, 1820, and evi. These include meiotic resumption, 2pb extrusion, pn formation and the initiation of.

We discuss the hypothesis that neither inactivation nor activation of a mekerk pathway is required for s phase completion in sea urchin egg. At a biochemical level, oocyte maturation is controlled by p42 mapk and cyclin bcdc2. Its activity was determined during oocyte maturation in vitro by the phosphorylation of its. Xenopus oocyte maturation requires the phosphorylation and activation of p42 mitogen activated protein kinase mapk. Cb 1 activation during oocyte maturation modulates akt and erk12 signaling.

Conversely, the injection of goldfish cmos antisense rna inhibited both mos synthesis and mapk activation in the 17. Differential inactivation of maturationpromoting factor. Leptin and mitogenactivated protein kinase mapk in oocytes. Analysis of individual oocytes showed that the response of mapk to. Morerecently, mitogenactivated protein kinase mapk,whichis highly activated throughout oocyte maturation 812, has been identified as one of the major downstream targets of mos 17.

Cb cannabinoid receptor drives oocyte maturation and. Injection of constitutively active xenopus cmos mrna into immature goldfish oocytes induced mapk activation, but neither mpf activation nor gvbd occurred. Obox4silencingactivated stat3 and mpf mapk signaling accelerate nuclear membrane breakdown in mouse oocytes. The p38 mapk is a member of the mitogen activated protein kinase mapk family that participates in a signaling cascade in response to cytokines and stress in somatic cells.

A positivefeedbackbased bistable memory module that. We provide evidence that a mitogen activated protein kinase mapk cascade couples maternal mrna translation to meiotic cell cycle progression in mouse oocytes by triggering cpeb1 phosphorylation and degradation. Mapk, to investigate the possible functional role of p38. Active mapk leads to maturationpromoting factor mpf activation and oocyte maturation and also activates a positivefeedback loop that enhances translation and stabilization of mos. In oocytes treated with the mek1 inhibitor u0126, the mapk pathway does not become activated, and bub1 remains in. Such oscillations inactivate the maturationpromoting factor mpf and the mitogenactivated protein kinase mapk, triggering the early events of oocyte activation and embryo development. Our data show that a novel, germlinespecific mapk pathway is required during oogenesis in several processes, including having an important role in the patterning of the egg. Mouse oocytes begin to mature in vitro once liberated from ovarian follicles.

The mapk pathway triggers activation of nek2 during. Nov 15, 2000 mek1 is present in immature mouse oocytes. By 2 h postelectroporation, mapk activity in the oocytes activated by electroporation plus cycloheximide 0. This report examines whether it also plays a role in normal mitotic progression. Nov 16, 2010 if this twostep activation model is correct, mapk, cdc2, and rsk each may be able to both partially activate cdc25c and generate primed cdc25c for the secondary phosphorylation and full activation during xenopus oocyte maturation. As you may already know, fertilization is the fusion of the male and female gametes. Cb1 cannabinoid receptor drives oocyte maturation and. The p42 mitogenactivated protein kinase mapk is required for progression through meiotic m phase in xenopus oocytes. P mapk, phosphorylated mitogenactivated protein kinase. The inhibition of mouse oocyte gvbd is due to the activation of pkc. It also appears that an oocyte dependent pathway downstream from oocyte enabled activation of mapk, and distinct from that promoting the. By enabling gonadotropindependent mapk activation in granulosa cells, oocytes promote the generation of a return signal from these cells that. Dptreated oocytes, but these oocytes underwent gvbd. Mitogenactivated protein kinase mapk is a family of serthr protein kinases that are widely distributed in eukaryotic cells.

In mammalian oocytes, mapk is activated during maturation but oocytes from cmos knockout mice, in which mapk is not activated, can undergo gvbd. Oocytedependent activation of mitogenactivated protein. Initiation of xenopus oocyte maturation by activation of. Mitogen activated protein kinase plays a significant role. In this report, we demonstrate that the synthesis and activation of mos are two separable processes. In oocytes undergoing full activation defined as pronuclear formation, mpf inactivation occurred more quickly and preceded mapk inactivation. In many cell types, the mitogenactivated protein kinase mapk also named extracellular signalregulated kinase erk is activated in response to a variety of extracellular growth factorreceptor interactions and leads to the transcriptional activation of immediate early genes, hereby influencing a number of tissuespecific biological activities, as cell proliferation, survival and. Read oocyte dependent activation of mitogen activated protein kinase erk12 in cumulus cells is required for the maturation of the mouse oocyte cumulus cell complex, developmental biology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Oocyte or ovumegg activation is a series of processes that occur in the oocyte during fertilization sperm entry causes calcium release into the oocyte. Both of these protein kinases are activated during maturation.

Molecular triggers of egg activation at fertilization in mammals in. Inactivation of mapk in mature oocytes triggers progression into. Prior to activation, mapk activity in mature oocyte was 0. The biochemical basis of an allornone cell fate switch in. Luteinizing hormone lh induces maturational processes in oocyte cumulus cell complexes occ of preovulatory follicles that include both resumption of meiosis in the oocyte and expansion mucification of the cumulus oophorus. Oocyte or ovum egg activation is a series of processes that occur in the oocyte during fertilization. A link between map kinase and p34cdc2cyclin b during oocyte. However, the signal that triggers cpeb1 activation at the onset of mammalian oocyte maturation is not known. Furthermore, other intracellular signal transducers, such as camp, protein kinase c and protein phosphotase, ect. While mos protein kinase has been reported to be essential for reentry into meiosis in xenopus, arrested oocytes can undergo germinal vesicle breakdown gvbd independently of mapk activation. The function of mitogenactivated protein kinase mapk during porcine oocyte maturation was examined by injecting oocytes with either mrna or antisense rna of. Nov 01, 2003 read oocytedependent activation of mitogenactivated protein kinase erk12 in cumulus cells is required for the maturation of the mouse oocytecumulus cell complex, developmental biology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.

Oocytedependent activation of mitogenactivated protein kinase. Requirement for mapk activation for normal mitotic. We provide evidence that a mitogenactivated protein kinase mapk cascade couples maternal mrna translation to meiotic cell cycle progression in mouse oocytes by triggering cpeb1 phosphorylation and degradation. In maturing starfish oocytes, mapk is activated only after mpf activation and gvbd. Mitogenactivated protein kinase mapk is a family of serthr protein kinases expressed widely in eukaryotic cells. By enabling gonadotropindependent mapk activation in granulosa cells, oocytes promote the generation of a return signal from these cells that induces the resumption of meiosis. In many cell types, the mitogen activated protein kinase mapk also named extracellular signalregulated kinase erk is activated in response to a variety of extracellular growth factorreceptor interactions and leads to the transcriptional activation of immediate early genes, hereby influencing a number of tissuespecific biological activities, as cell proliferation, survival and. Leptin enhances oocyte nuclear and cytoplasmic maturation via. Mitogenactivated protein kinase phosphorylation patterns in. The resumption of meiosis in xenopus arrested oocytes is triggered by progesterone, which leads to polyadenylation and translation of mos mrna, then activation of mapk pathway.

Changes in mpf and mapk activities during ia and sa of rat oocytes. Interference with mapk activation by immunodepletion. Consistent with this, ectopic activation of mapk in immature rana oocytes with constitutive active ste11 protein also fails to initiate maturation. Participation of mapk, pka and pp2a in the regulation of mpf. The mos protein is required for the activation and stabilization of m phasepromoting factor mpf, the master of cell cycle switch, through a pathway that involves the mitogenactivated protein. Fortunately, sperminduced oocyte activation can be mimicked by a variety of chemicals as well as by electrical stimulation 17, which allows precise control of the timing of activation. Oocyte maturation, which involves germinal vesicle breakdown, progression through metaphase i mi, and arrest at mii, is triggered and regulated by the coordinated action of two kinases, maturation promoting factor mpf and mitogen activated protein kinase mapk. In addition, rsk contributes to metaphase ii arrest, by activation of either bub1 or an as yet unkown csf pathway, which inhibits the anaphasepromoting complex apcc. Mek in turn activates erktype mapk and downstream effectors that maintain mphase promoting factor mpf activity 1416. Moreover, inhibition of erk activation partially inhibits t48 phosphorylation, activation of hcdc25c and mitotic induction. This suggests an important role for the p34 cdc2 inhibitory kinases such as wee1 and myt1 in regulating the g 2 m transition during oocyte maturation.

In immunoblots, p38 mapk was detected in oocytes and cumulus cells. The mosmapk pathway is involved in metaphase ii arrest as. These low levels of mapk activation correlated with low levels of cdc25 phosphorylation figure s5b, and inhibiting mapk activation inhibited cdc25 phosphorylation and activation figure 6f. Mapk activity in oocytes and cumulus cells to examine the kinetics of gonadotropininduced oocyte meiotic resumption and mapk activation in both oocytes and cumulus cells in vivo, mos or mos female mice were injected with hcg 5 iu mouse. Xenopus oocytes convert a continuously variable stimulus, the concentration of the maturationinducing hormone progesterone, into an allornone biological responseoocyte maturation. Both isoforms of mapk were unphosphorylated in oocytes recovered immediately after liberation from follicles and became phosphorylated following 25. Both isoforms of mapk were unphosphorylated in oocytes recovered immediately after liberation from follicles and became phosphorylated. Mii arrest persists until fertilization or parthenogenetic egg activation, when the egg. Aug 01, 2004 the p38 mapk is a member of the mitogenactivated protein kinase mapk family that participates in a signaling cascade in response to cytokines and stress in somatic cells. Rat oocytes are well known to undergo spontaneous activation sa after leaving the oviduct, but the sa is abortive with oocytes being arrested in metaphase iii miii instead of forming pronuclei. Activation of p38 mapk during porcine oocyte maturation1 biology. Activation of p38 mapk during porcine oocyte maturation1. Oocyte activation is an essential process induced by sperm entry, converting a mature arrested oocyte into a fertilized oocyte.