Role of Src homology 2 domain-mediated PTK signaling in mouse zygotic development

Meng, Lingjun; Luo, Jinping; Li, Chunhua; Kinsey, William H.

doi:10.1530/rep.1.01151

Cited by 27 publications

(45 citation statements)

References 47 publications

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“…Our recent studies have focused on the role of SFKs during oocyte maturation and fertilization [10,11,14]. The present data reinforce a role for Fyn kinase in what we suggest is an example of cortical maturation.…”

Section: Intracellular Localization and Dynamics Of Protein Phosphorysupporting

confidence: 87%

“…Fyn knock-out oocytes fail to increase cortical phosphorylation of pTyr proteins Our studies of SFKs during meiotic maturation and fertilization have demonstrated an essential function for SFKs for proper organization of chromosomes and spindles [10,11,14]. Of the nine SFKs produced in mammalian cells, FYN kinase is expressed at very high levels in oocytes.…”

Section: Patterns Of Mpm2mentioning

confidence: 99%

“…While ser/thr kinases are well known to drive the meiotic cell cycle, only recently has it become apparent that tyrosine kinases are also essential components in the process of oocyte maturation and early development in mammals. For example, Src-family kinases (SFKs) appear to mediate meiotic spindle and chromatin modifications in rodent oocytes [10][11][12][13][14]. Until the interplay between discrete protein kinase signaling pathways can be resolved in mammalian oocytes, the role of these factors in determining the quality of oocyte nuclear and cytoplasmic maturation will remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of protein phosphorylation during meiotic maturation

McGinnis

Albertini

2010

J Assist Reprod Genet

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Purpose To ask whether distinct kinase signaling pathways mediate cytoplasmic or nuclear maturation of mouse oocytes and if in vitro maturation influences the distribution and timing of these phosphorylation events. Methods Mouse cumulus oocyte complexes (COCs) were matured under conditions known to influence oocyte quality (basal or supplemented media) and assayed with epitope specific antibodies that would distinguish between Cdk1 or tyrosine kinase targets at 0, 2, 4, 8, and 16 hrs. Semi-quantitative image analysis was used to assess the topographical patterns of protein phosphorylation during in vitro maturation. In vitro fertization and embryo culture were used to examine the effects of culture conditions on developmental potential. Results Protein tyrosine phosphorylation increased during meiotic progression from methaphase-I to metaphase-II. Levels were significantly higher in the oocyte cortex. Levels of cortical staining are enhanced in oocytes matured in supplemented media that displayed higher developmental competence. In contrast, bulk substrates for Cdk1 kinase localize to the meiotic spindle while cytoplasmic levels of kinase activity increase throughout meiotic progression; culture media had no measurable effect. Ablation of the tyrosine kinase Fyn significantly reduced cortical levels of tyrosine phosphorylation. Conclusions The findings indicate that distinct signaling pathways mediate nuclear and cytoplasmic maturation during in vitro maturation in a fashion consistent with a role for tyrosine kinases in cortical maturation and oocyte quality.

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Section: Intracellular Localization and Dynamics Of Protein Phosphorysupporting

confidence: 87%

Section: Patterns Of Mpm2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamics of protein phosphorylation during meiotic maturation

McGinnis

Albertini

2010

J Assist Reprod Genet

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“…Src, Yes, and Fyn are found in a broad range of mammalian cells, including oocytes (Sato et al 1996, Talmor-Cohen et al 2004, Mehlmann & Jaffe 2005, Meng et al 2006, McGinnis et al 2007, Zheng et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis

Levi¹,

Maro²,

Shalgi³

2010

Reproduction

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Fertilization of mammalian oocytes triggers their exit from the second meiotic division metaphase arrest. The extrusion of the second polar body (PBII) that marks the completion of meiosis is followed by the first mitotic cleavage of the zygote. Several lines of evidence in somatic cells imply the involvement of Fyn, an Src family kinase (SFK), in cell cycle control and actin functions. In this study, we demonstrate, using live cell confocal imaging and microinjection of Fyn cRNAs, the recruitment of Fyn to the oocyte's cortical area overlying the chromosomes and its colocalization with filamentous actin (F-actin) during exit from the meiotic metaphase. Fyn concentrated asymmetrically at the cortical site designated for ingression of the PBII cleavage furrow, where F-actin had already been accumulated, and then redispersed throughout the entire cortex only to be recruited again to the cleavage furrow during the first mitotic division. Although microinjection of dominant negative Fyn did not affect initiation of the cleavage furrow, it prolonged the average duration of ingression, decreased the rates of PB extrusion and of the first cleavage, and led to the formation of bigger PBs and longer spindles. Extrusion of the PBII was blocked in oocytes exposed to SU6656, an SFK inhibitor. Our results demonstrate, for the first time, a continuous colocalization of Fyn and F-actin during meiosis and imply a role for the SFKs, in general, and for Fyn, in particular, in regulating pathways that involve actin cytoskeleton, during ingression of the meiotic and mitotic cleavage furrows.

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“…Similarly, SFKs mediate the fertilization-induced Ca 2+ response of the frog Xenopus (Sato et al 2000(Sato et al , 2006, albeit by different mechanisms than in other deuterostomes (Runft et al 2002). Conversely, although mammalian eggs express SFKs, such kinases are apparently not necessary for initiating Ca 2+ oscillations (Kurokawa et al 2004;Mehlmann and Jaffe 2005;Meng et al 2006;Tomashov-Matar et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Roles of Src family kinase signaling during fertilization and the first cell cycle in the marine protostome worm Cerebratulus

Stricker

Carroll²,

Tsui³

2010

Int. J. Dev. Biol.

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For eggs to generate a calcium response during fertilization, the sperm of many deuterostome animals must first activate a group of egg kinases, called Src family kinases (SFKs). However, whether SFK activation is also required for fertilization-induced calcium signals in eggs of protostomes remains unknown. Thus, in this study, unfertilized oocytes of the marine protostome worm Cerebratulus were treated with either PP2 to inhibit SFKs or with U73122 to block phospholipase C activity downstream of SFK. Compared with control fertilizations, the inhibitors significantly reduced post-insemination levels of polar body formation and cleavage, but apparently did so via different mechanisms, based on the variable effects of these drugs on sperm incorporations and pronuclear differentiation. Moreover, confocal calcium imaging revealed that repetitive calcium waves (=oscillations) were blocked by U73122, but not by PP2, even though immunoblots indicated SFK activity was inhibited by PP2. Such findings fail to support the view that SFKs are required for initiating fertilization-induced calcium oscillations in Cerebratulus, and alternative mechanisms for the observed inhibition of polar body formation and cleavage in drug-treated specimens are discussed.

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Role of Src homology 2 domain-mediated PTK signaling in mouse zygotic development

Cited by 27 publications

References 47 publications

Dynamics of protein phosphorylation during meiotic maturation

Dynamics of protein phosphorylation during meiotic maturation

Fyn kinase is involved in cleavage furrow ingression during meiosis and mitosis

Roles of Src family kinase signaling during fertilization and the first cell cycle in the marine protostome worm Cerebratulus

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