IGF-I and FGF-2 coordinately enhance cyclin D1 and cyclin E-cdk2 association and activity to promote G1 progression in oligodendrocyte progenitor cells
IGF-I and FGF-2 coordinately enhance cyclin D1 and cyclin E-cdk2 association and activity to promote G1 progression in oligodendrocyte progenitor cells
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DOI：
10.1016/j.mcn.2003.11.015
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发表时间：
2004-03-01
影响因子：
3.5
通讯作者：
Wood, TL
中科院分区：
文献类型：
--
作者：
Frederick, TJ;Wood, TL
发育神经生物学中的一个关键问题是干细胞和祖细胞如何解释多种信号以决定是否增殖或退出细胞周期。胰岛素样生长因子（IGF）-I和成纤维细胞生长因子（FGF）-2分别在神经干细胞以及更有限的神经元和神经胶质祖细胞的发育中具有已知的功能。本研究的目的是阐明IGF-I和FGF-2如何协调调节原代少突胶质祖细胞（OP）的细胞周期机制。IGF-I/FGF-2协同增加OP细胞募集进入S期的数量。IGF-I增强FGF-2对细胞周期蛋白D1的诱导、G（1）细胞周期蛋白-细胞周期蛋白依赖性激酶（cdk）复合物的激活和视网膜母细胞瘤蛋白（pRb）的过度磷酸化。此外，IGF-I是G（2）/M进展所必需的。相比之下，FGF-2降低了与细胞周期蛋白E-cdk 2相关的cdk抑制剂p27（Kip 1）的水平。这些研究为多种生长因子协调调节祖细胞的细胞周期进程提供了机制基础。爱思唯尔公司出版
A critical question in developmental neurobiology is how stem and progenitor cells interpret multiple signals to decide whether to proliferate or exit the cell cycle. Insulin-like growth factor (IGF)-I and fibroblast growth factor (FGF)-2 have known functions individually in development of neural stem cells as well as more restricted neuronal and glial progenitor cells. The goal of this study was to elucidate how IGF-I and FGF-2 coordinately regulate the cell cycle machinery in primary oligodendrocyte progenitors (OPs). IGF-I/FGF-2 synergistically increased the numbers of OP cells recruited into S phase. IGF-I enhanced FGF-2 induction of cyclin D1, activation of G(1) cyclin-cyclin-dependent kinase (cdk) complexes, and hyperphosphorylation of retinoblastoma protein (pRb). Moreover, IGF-I was required for G(2)/M progression. In contrast, FGF-2 decreased levels of the cdk inhibitor p27(Kip1) associated with cyclin E-cdk2. These studies provide a mechanistic basis for coordinate regulation of cell cycle progression in progenitor cells by multiple growth factors. Published by Elsevier Inc.