Tyrosine phosphorylation profiling in FGF-2 stimulated human embryonic stem cells.
Tyrosine phosphorylation profiling in FGF-2 stimulated human embryonic stem cells.
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DOI：
10.1371/journal.pone.0017538
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发表时间：
2011-03-17
期刊：
影响因子：
3.7
通讯作者：
Choo A
中科院分区：
文献类型：
--
作者：
Ding VM;Boersema PJ;Foong LY;Preisinger C;Koh G;Natarajan S;Lee DY;Boekhorst J;Snel B;Lemeer S;Heck AJ;Choo A
使用靶向磷酸蛋白质组学方法研究成纤维细胞生长因子-2（FGF-2）在维持未分化的人胚胎干细胞（hESC）中的作用，以特异性分析FGF-2刺激后的酪氨酸磷酸化事件。在430个蛋白质上鉴定了735个独特的酪氨酸磷酸化位点的累积总数，这是迄今为止人类胚胎干细胞的最大库存。FGF-2刺激的人胚胎干细胞的早期信号事件进行了定量监测，使用稳定的同位素二甲基标记，导致316个独特的磷酸酪氨酸肽来源于188种蛋白质的时间酪氨酸磷酸化的配置文件。除了所有四种FGF受体的快速激活外，还观察到几种其他受体酪氨酸激酶（RTK）的反式激活以及下游蛋白如PI 3-K、MAPK和几种Src家族成员的诱导酪氨酸磷酸化。PI 3-K和MAPK均通过FGF-2介导的信号传导与hESC维持相关。所观察到的FGF-2对Src激酶家族成员的激活和Src激酶抑制后多能标记物表达的丧失可能指向细胞骨架和肌动蛋白依赖性过程的调节以维持未分化的hESC。
The role of fibroblast growth factor-2 (FGF-2) in maintaining undifferentiated human embryonic stem cells (hESC) was investigated using a targeted phosphoproteomics approach to specifically profile tyrosine phosphorylation events following FGF-2 stimulation. A cumulative total number of 735 unique tyrosine phosphorylation sites on 430 proteins were identified, by far the largest inventory to date for hESC. Early signaling events in FGF-2 stimulated hESC were quantitatively monitored using stable isotope dimethyl labeling, resulting in temporal tyrosine phosphorylation profiles of 316 unique phosphotyrosine peptides originating from 188 proteins. Apart from the rapid activation of all four FGF receptors, trans-activation of several other receptor tyrosine kinases (RTKs) was observed as well as induced tyrosine phosphorylation of downstream proteins such as PI3-K, MAPK and several Src family members. Both PI3-K and MAPK have been linked to hESC maintenance through FGF-2 mediated signaling. The observed activation of the Src kinase family members by FGF-2 and loss of pluripotent marker expression post Src kinase inhibition may point to the regulation of cytoskeletal and actin depending processes to maintain undifferentiated hESC.
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影响因子：
3.7
作者：
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