Molecular dissection of egg fertilization signaling with the aid of tyrosine kinase-specific inhibitor and activator strategies

Molecular dissection of egg fertilization signaling with the aid of tyrosine kinase-specific inhibitor and activator strategies
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DOI:
10.1016/j.bbapap.2003.11.017
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发表时间:
2004-03-11
影响因子:
3.2
通讯作者:
Fukami, Y
Fukami, Y
中科院分区:
生物学3区
文献类型:
--
作者:
Sato, K;Iwasaki, T;Fukami, Y

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受精是由精卵相互作用与融合触发的,这会引发细胞内游离钙离子([Ca2+]i)短暂升高,而这一系列生化和细胞生物学事件被称为“卵子激活”。依赖钙离子的卵子激活会启动发育程序,最终个体诞生。越来越多的知识在一定程度上揭示了精子诱导[Ca2+]i短暂升高背后的分子机制;也就是说,在目前研究的大多数动物中,第二信使1,4,5 - 三磷酸肌醇(IP3)似乎在受精时诱导[Ca2+]i短暂变化中起着关键作用。然而,精子启动IP3 - [Ca2+]i短暂通路所使用的信号机制尚未阐明。为了解决这个问题,我们采用非洲爪蟾(Xenopus laevis)作为模式动物,并专门设计实验来确定Src家族蛋白酪氨酸激酶(SFKs或Src家族PTKs)在精子诱导的卵子激活中的作用。本综述汇集了有关使用PTK特异性抑制剂和激活剂来分析卵子受精过程中信号转导事件的信息。具体而言,我们聚焦于爪蟾Src的分子鉴定以及最近确立的依赖Src的卵子激活的信号机制。我们还总结了在理解Src家族激酶在其他模式生物卵子受精中的作用方面的最新进展,并讨论了该领域未来的发展方向。(C)2003爱思唯尔出版社保留所有权利。
Fertilization is triggered by sperm-egg interaction and fusion that initiate a transient rise(s) in the free intracellular calcium ([Ca2+](i)) that is responsible for a series of biochemical and cell biological events, so-called "egg activation". Calcium-dependent egg activation leads to the initiation of developmental program that culminates in the birth of individuals. A growing body of knowledge has uncovered the molecular mechanisms underlying sperm-induced transient [Ca2+](i) increase(s) to some extent; namely, in most animals so far studied, a second messenger mositol 1,4,5-trisphosphate (IP3) seems to play a pivotal role in inducing [Ca2+](i) transient(s) at fertilization. However, signaling mechanisms used by sperm to initiate IP3-[Ca2+](i) transient pathway have not been elucidated, To approach this problem, we have employed African clawed frog, Xenopus laevis, as a model animal and conducted experiments designed specifically to determine the role of the Src family protein-tyrosine kinases (SFKs or Src family PTKs) in the sperm-induced egg activation. This review compiles information about the use of PTK-specific inhibitors and activators for analyzing signal transduction events in egg fertilization. Specifically, we focus on molecular identification of Xenopus Src and the signaling mechanism of the Src-dependent egg activation that has been established recently. We also summarize recent advances in understanding the role of the Src family kinases in egg fertilization of other model organisms, and discuss future directions of the field. (C) 2003 Elsevier B.V All rights reserved.