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Biphasic Activation of Aurora-A Kinase during the Meiosis I- Meiosis II Transition in Xenopus Oocytes

机译:爪蟾卵母细胞减数分裂I-减数分裂II过渡期间Aurora-A激酶的双相激活

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Xenopus Aurora-A (also known as Eg2) is a member of the Aurora family of mitotic serine/threonine kinases. In Xenopus oocytes, Aurora-A phosphorylates and activates a cytoplasmic mRNA polyadenylation factor (CPEB) and therefore plays a pivotal role in MOS translation. However, hyperphosphorylation and activation of Aurora-A appear to be dependent on maturation-promoting factor (MPF) activation. To resolve this apparent paradox, we generated a constitutively activated Aurora-A by engineering a myristylation signal at its N terminus. Injection of Myr-Aurora-A mRNA induced germinal vesicle breakdown (GVBD) with the concomitant activation of MOS, mitogen-activated protein kinase, and MPF. Myr-Aurora-A-injected oocytes, however, appeared to arrest in meiosis I with high MPF activity and highly condensed, metaphase-like chromosomes but no organized microtubule spindles. No degradation of CPEB or cyclin B2 was observed following GVBD in Myr-Aurora-A-injected oocytes. In the presence of progesterone, the endogenous Aurora-A became hyperphosphorylated and activated at the time of MPF activation. Following GVBD, Aurora-A was gradually dephosphorylated and inactivated before it was hyperphosphorylated and activated again. This biphasic pattern of Aurora-A activation mirrored that of MPF activation and hence may explain meiosis I arrest by the constitutively activated Myr-Aurora-A.
机译:非洲爪蟾 Aurora-A(也称为Eg2)是Aurora有丝分裂丝氨酸/苏氨酸激酶家族的成员。在非洲爪蟾卵母细胞中,Aurora-A磷酸化并激活细胞质mRNA聚腺苷酸化因子(CPEB),因此在 MOS 翻译中起关键作用。但是,Aurora-A的过度磷酸化和激活似乎取决于成熟促进因子(MPF)的激活。为了解决这一明显的矛盾,我们通过在其N端工程化肉豆蔻化信号来生成组成型激活的Aurora-A。注入Myr-Aurora-A mRNA会导致生小泡破裂(GVBD),同时伴随MOS激活,丝裂原激活的蛋白激酶和MPF。然而,注入Myr-Aurora-A的卵母细胞似乎停滞在具有高MPF活性和高度浓缩的中期样染色体的减数分裂I中,但没有组织的微管纺锤体。在注入Myr-Aurora-A的卵母细胞中进行GVBD后,未观察到CPEB或细胞周期蛋白B2的降解。在孕酮存在下,内源性Aurora-A在MPF激活时被过度磷酸化并被激活。在GVBD之后,Aurora-A逐渐被去磷酸化和失活,然后被超磷酸化并再次被激活。 Aurora-A激活的这种双相模式与MPF激活相类似,因此可以解释减数分裂I被组成型激活的Myr-Aurora-A阻滞。

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