PKB/AKT is involved in resumption of meiosis in mouse oocytes

Kalous, Jaroslav; Solc, P; Baran, Vladimı́r; Kubelka, Michal; Schultz, Richard M.; Motlı́k, Jan

doi:10.1042/bc20050020

Cited by 97 publications

(114 citation statements)

References 48 publications

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“…TOR-dependent phosphorylation of Akt in starfish oocytes Akt activation has previously been reported in mouse and bovine oocytes (Tomek and Smiljakovic, 2005;Kalous et al, 2006); however our present observations represent the first indication that the TOR protein is required for the phosphorylation of both the TM and HM in oocytes. Although other components of the sfTOR complex remain to be identified, TORC2 rather than TORC1 is likely responsible for phosphorylation of both sites in starfish oocytes (Figure 2c, Supplementary Figures S3c-e).…”

Section: Mutual Phosphorylation Of Akt On Conserved Motifs D Hiraoka supporting

confidence: 64%

Turn motif phosphorylation negatively regulates activation loop phosphorylation in Akt

2011

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Akt, also known as protein kinase B, has a central role in various signaling pathways that regulate cellular processes such as metabolism, proliferation and survival. On stimulation, phosphorylation of the activation loop (Aloop) and hydrophobic motif (HM) of Akt by the kinase phosphoinositide-dependent kinase 1 (PDK1) and the mammalian target of rapamycin complex 2 (mTORC2), respectively, results in Akt activation. A well-conserved threonine in the turn motif (TM) is also constitutively phosphorylated by mTORC2 and contributes to the stability of Akt. The role of TM phosphorylation in HM and A-loop phosphorylation has not been sufficiently evaluated. Using starfish oocytes as a model system, this study provides the first evidence that TM phosphorylation has a negative role in A-loop phosphorylation. In this system, the maturation-inducing hormone, 1-methyladenine, stimulates Akt to reinitiate meiosis through activation of cyclin B-Cdc2. The phosphorylation status of Akt was monitored via introduction of exogenous human Akt (hAkt) in starfish oocytes. TM and HM phosphorylation was inhibited by microinjection of an anti-starfish TOR antibody, but not by rapamycin treatment, suggesting that both phosphorylation events depend on TORC2, as reported in mammalian cells. A single or double alanine substitution at each of three phosphorylation residues revealed that TM phosphorylation renders Akt susceptible to dephosphorylation on the A-loop. When A-loop phosphatase was inhibited by okadaic acid (OA), TM phosphorylation still reduced Aloop phosphorylation, suggesting that the effect is caused at least partially through reduction of sensitivity to PDK1. Negative regulation by TM phosphorylation was also observed in constitutively active Akt and was functionally reflected in meiosis resumption. By contrast, HM phosphorylation enhanced A-loop phosphorylation and achieved full activation of Akt via a mechanism at least partially independent of TM phosphorylation. These observations provide new insight into the mechanism controlling Akt phosphorylation in the cell.

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Section: Mutual Phosphorylation Of Akt On Conserved Motifs D Hiraoka supporting

confidence: 64%

Turn motif phosphorylation negatively regulates activation loop phosphorylation in Akt

2011

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“…4H) in Cox-2 Ϫ/Ϫ females, we further asked whether these processes under the influence of PGE 2 utilize differential signaling cas- cades during oocyte maturation. Early studies have demonstrated that cumulus expansion in response to gonadotropin or other stimuli depends on multiple signaling pathways, including cAMP/PKA (42-45), ERK1/2 (34, 46 -49), p38 MAPK (34,49), as well as PI3K-Akt signaling (40,41). Thus, we next used selective antagonists of these pathways and tested their effects under PGE 2 stimulation in cumulus cells.…”

Section: Pge 2 Directs Cumulus Cell Expansion and Survival During Oocmentioning

confidence: 99%

“…Increasing evidence points toward the involvement of the PI3K-Akt signaling cascade in gonadotropin-induced oocyte meiotic maturation (40,41). Thus, we first examined the expression of phospho-Akt in COCs in wild-type and Cox-2 Ϫ/Ϫ mice during in vivo oocyte maturation.…”

Section: Pge 2 Directs Cumulus Cell Expansion and Survival During Oocmentioning

confidence: 99%

Cyclooxygenase-2-derived Prostaglandin E2 Directs Oocyte Maturation by Differentially Influencing Multiple Signaling Pathways

Takahashi

Morrow

Wang

et al. 2006

Journal of Biological Chemistry

130

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The process of oocyte maturation, which impacts ovulation and fertilization, is complex and requires an integration of the endocrine, paracrine, juxtacrine, and autocrine signaling pathways. This process involves an intimate interaction between the oocyte and encircling cumulus cells within a follicle, a unique venue for somatic and germ cell communication. Cumulus cell expansion and resumption of meiosis with germinal vesicle breakdown are major events in oocyte maturation. Cyclooxygenase-2 (COX-2)-derived prostaglandin E 2 (PGE 2 ) is a known critical mediator of oocyte maturation, but the diverse function of this lipid mediator in oocyte maturation, ovulation, and fertilization has not been fully appreciated. We show here that gonadotropins in coordination with PGE 2 signaling via its cell surface G-protein-coupled EP2 and EP4 receptor subtypes direct cumulus cell expansion and survival and oocyte meiotic maturation by differentially impacting cAMPdependent protein kinase, MAPK, NF-B, and phosphatidylinositol 3-kinase/Akt pathways. This study is unique in the sense that it provides evidence for new site-and event-specific involvement of these signaling pathways under the influence of COX-2-derived PGE 2 during the critical stages of this somatic-germ cell interaction, an absolute requirement for oocyte maturation. Prostaglandins (PGs)4 are involved in various female reproductive functions, including ovulation, fertilization, and implantation (1, 2). The cyclooxygenase (COX)

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“…At GVBD, phosphorylated PKB has been observed on the centrosome. This result shows that one function of PKB is to initiate the activation of CDK1 [29]. Furthermore, while the mechanism of PKB activation in mouse oocytes is not understood, it may be linked to the ability of high levels of cAMP to inhibit PKB activity [4].…”

Section: Gvbd or Resumption Of The First Meiosismentioning

confidence: 95%

“…PKB is likely involved in the maturation of oocytes, probably independent of MPF activation. A peak in PKB activity has been observed at approximately the time of GVBD and activity of PKB declined at MI in pig oocytes [29]. Kalous et al [29] found that PKB is related to CDK1 activation and participates in resumption of meiosis in mouse oocytes.…”

Section: Gvbd or Resumption Of The First Meiosismentioning

confidence: 99%

Protein Profile Involved in Mammalian Oocyte Maturation, Fertilization and Early Embryogenesis (Pre-Implantation)

Turathum¹,

Sroyraya²

2017

Cell Dev Biol

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Proteomic analysis of oocytes can help identify proteins that are involved in female meiotic maturation and early embryonic development. Many proteins with well-defined functions have been identified during oocyte maturation. High levels of MPF, MAPK, Mos and low levels of cAMP play an essential role in the resumption of meiosis I. Following germinal vesicle breakdown, chromosome condensation and spindle formation occurred at metaphase I by assembly of the meiotic apparatus, which includes the proteins NuMA, γ-tubulin and Polo-like kinase 1. The metaphase II arrest is a result of high levels of MPF and MAPK. Proteins involved in the stress response and redox regulation, including peroxiredoxin, GST and HSF1, are also necessary for protection against oxidative stress. During fertilization, the sperm-egg interaction requires egg surface proteins, oocyte zona pellucida, molecular chaperones, GPI-anchored proteins and CD9 to recognize sperm proteins and prevent polyspermy. Following gamete fusion, resumption and complete of meiosis II is induced by GTP and CaM kinase II activation, which inactivates MPF and activation of the anaphase promoting complex/cyclosome results in sister chromatid separation. Decondensation of the sperm head begins after zona penetration and GSH and NPM2 are necessary for male pronuclear formation. MAPK inactivation is required for pronuclear formation. At the cleavage stage, the maternal effect proteins PADI6, FLOPED and FILIA are essential for embryonic progression past the two-cell stage. After cell adhesion, cell junctions and the cytoskeleton play an important role in compaction of the morula. Par6, Par3 and protein kinase C are components of the apical polarity complex and are important for formation of the blastocoel cavity. During the blastocyst stage, TEAD4 and CDX2 are required for trophoectoderm formation. This proteomic analysis of oocytes has improved our understanding of the molecular processes that regulate oocyte maturation, fertilization and pre-implantation in mammals.

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PKB/AKT is involved in resumption of meiosis in mouse oocytes

Cited by 97 publications

References 48 publications

Turn motif phosphorylation negatively regulates activation loop phosphorylation in Akt

Turn motif phosphorylation negatively regulates activation loop phosphorylation in Akt

Cyclooxygenase-2-derived Prostaglandin E2 Directs Oocyte Maturation by Differentially Influencing Multiple Signaling Pathways

Protein Profile Involved in Mammalian Oocyte Maturation, Fertilization and Early Embryogenesis (Pre-Implantation)

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