Signaling through extracellular signal-regulated kinase is required for spermatogonial proliferative response to stem cell factor
Signaling through extracellular signal-regulated kinase is required for spermatogonial proliferative response to stem cell factor
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DOI：
10.1074/jbc.m105143200
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发表时间：
2001-10-26
影响因子：
4.8
通讯作者：
Rossi, P
中科院分区：
文献类型：
--
作者：
Dolci, S;Pellegrini, M;Rossi, P
在体外将干细胞因子（SCF）加入到表达c-kit的A（1）-A（4）的青春期前小鼠精原细胞中，可刺激其进入有丝分裂细胞周期，并显著减少这些细胞的凋亡。添加SCF会导致细胞外信号调节激酶（Erk）1/2以及磷脂酰肌醇3-激酶（PI 3 K）依赖性Akt激酶的瞬时激活。这些事件之后是细胞周期蛋白D3的快速重新分布，其主要是核，而其总细胞量不变。细胞周期蛋白D3的核积累与相关激酶活性的瞬时激活相耦合，使用视网膜母细胞瘤蛋白（Rb）作为底物进行测定。这些事件之后是细胞周期蛋白E的瞬时积累，刺激相关的组蛋白HI-激酶活性，细胞周期蛋白A2的延迟积累和Rb过度磷酸化。所有与SCF诱导的细胞周期进展相关的事件都被PI 3 K抑制剂或丝裂原活化蛋白激酶激酶（MEK）抑制剂抑制，表明MEK和PI 3 K对c-kit介导的增殖反应至关重要。相反，SCF的抗凋亡作用不受单独添加MEK或PI 3 K抑制剂的影响。因此，SCF对表达c-kit的精原细胞的有丝分裂和存活的影响依赖于不同的信号转导途径。
In vitro addition of stem cell factor (SCF) to c-kit-expressing A(1)-A(4) spermatogonia from prepuberal mice stimulates their progression into the mitotic cell cycle and significantly reduces apoptosis in these cells. SCF addition results in a transient activation of extracellular signal-regulated kinases (Erk)1/2 as well as of phosphatidylinositol 3-kinase (PI3K)-dependent Akt kinase. These events are followed by a rapid redistribution of cyclin D3, which becomes predominantly nuclear, whereas its total cellular amount does not change. Nuclear accumulation of cyclin D3 is coupled to transient activation of the associated kinase activity, assayed using the retinoblastoma protein (Rb) as a substrate. These events were followed by a transient accumulation of cyclin E, stimulation of the associated histone HI-kinase activity, a delayed accumulation of cyclin A2, and Rb hyper-phosphorylation. All the events associated with SCF-induced cell cycle progression are inhibited by the addition of either a PI3K inhibitor or a mitogen-activated protein-kinase kinase (MEK) inhibitor, indicating that both MEK and PI3K are essential for c-kit-mediated proliferative response. On the contrary, the anti-apoptotic effect of SCF is not influenced by the separate addition of either MEK or PI3K inhibitors. Thus, SCF effects on mitogenesis and survival in c-kit expressing spermatogonia rely on different signal transduction pathways.