Quantitative analysis of brain nuclear phosphoproteins identifies developmentally regulated phosphorylation events.
Quantitative analysis of brain nuclear phosphoproteins identifies developmentally regulated phosphorylation events.
复制标题
DOI：
10.1021/pr8003198
复制
发表时间：
2008-11
影响因子：
4.4
通讯作者：
Yates, John R., III
中科院分区：
文献类型：
--
作者：
Liao, Lujian;McClatchy, Daniel B.;Park, Sung Kyu;Xu, Tao;Lu, Bingwen;Yates, John R., III
蛋白质磷酸化是一种全球广泛采用和严格控制的翻译后修饰，代表了控制整个生物过程的最重要的分子转换机制之一。在中枢神经系统中，已经证明介导染色质重塑和基因转录的关键蛋白的磷酸化在控制脑发育、突触发生、学习和记忆中起重要作用。许多研究集中在大规模鉴定脑组织中的磷酸肽。这些研究已经确定了用于预测蛋白激酶底物的磷酸化位点特异性基序。在这项研究中，我们采用了以前开发的定量方法，稳定同位素标记的氨基酸在哺乳动物（SILAM），以量化的变化，在核蛋白的磷酸化之间的出生后第一天（P1）和p45大鼠大脑皮层。使用15 N标记的大鼠大脑作为内标，我们定量705磷酸肽在p1皮层和1477磷酸肽在p45皮层，这转化为380和585磷酸蛋白在p1和p45皮层，分别。差异修饰的磷蛋白的生物信息学分析显示，磷酸化上调的多个组件的染色质重塑复合物在p1皮层。总之，我们首次证明了采用稳定同位素标记的大鼠组织进行全球定量磷酸化分析的有用性。
Protein phosphorylation is a globally adopted and tightly controlled post-translational modification, and represents one of the most important molecular switching mechanisms that govern the entire spectrum of biological processes. In the central nervous system, it has been demonstrated that phosphorylation of key proteins mediating chromatin remodeling and gene transcription plays an important role controlling brain development, synaptogenesis, learning and memory. Many studies have focused on large scale identification of phosphopeptides in brain tissue. These studies have identified phosphorylation site specific motifs useful for predicting protein kinases substrates. In this study, we applied a previously developed quantitative approach, stable isotope labeling of amino acids in mammals (SILAM), to quantify changes in the phosphorylation of nuclear proteins between a postnatal day one (p1) and a p45 rat brain cortex. Using a 15N labeled rat brain as an internal standard, we quantified 705 phosphopeptides in the p1 cortex and 1477 phosphopeptides in the p45 cortex, which translates to 380 and 585 phosphoproteins in p1 and p45 cortex, respectively. Bioinformatic analysis of the differentially modified phosphoproteins revealed that phosphorylation is upregulated on multiple components of chromatin remodeling complexes in the p1 cortex. Taken together, we demonstrated for the first time the usefulness of employing stable isotope labeled rat tissue for global quantitative phosphorylation analysis.
登录
查看更多内容
影响因子：
4
作者：
Huang, Haojie;Tindall, Donald J.
通讯作者：
Tindall, Donald J.
DOI：
10.1016/s1044-0305(98)00088-9
发表时间：
1998-11-01
影响因子：
3.2
作者：
DeGnore, JP;Qin, J
通讯作者：
Qin, J
影响因子：
48
作者：
Bodenmiller, Bernd;Mueller, Lukas N.;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
影响因子：
7.4
作者：
Conrads, TP;Alving, K;Smith, RD
通讯作者：
Smith, RD
影响因子：
14.9
作者：
DIGNAM, JD;LEBOVITZ, RM;ROEDER, RG
通讯作者：
ROEDER, RG