Identification of AMP-activated protein kinase targets by a consensus sequence search of the proteome.
Identification of AMP-activated protein kinase targets by a consensus sequence search of the proteome.
复制标题
通过对蛋白质组的共识序列搜索来鉴定AMP激活的蛋白激酶靶标。
DOI：
10.1186/s12918-015-0156-0
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发表时间：
2015-03-11
影响因子：
--
通讯作者：
Shyy JY
中科院分区：
文献类型：
--
作者：
Marin TL;Gongol B;Martin M;King SJ;Smith L;Johnson DA;Subramaniam S;Chien S;Shyy JY
AMP活化蛋白激酶（AMPK）是一种异源三聚体丝氨酸/苏氨酸蛋白激酶，其通过与ATP耗竭或应激相关的细胞扰动而活化。虽然AMPK调节含有特异性磷酸化共有序列的多种靶标的活性，但AMPK靶标的数量及其对细胞过程的影响目前被认为是有限的。我们查询了人类和小鼠蛋白质组中含有AMPK磷酸化共有序列的蛋白质。将该数据库整合到Gaggle软件中有助于基于已知和预测的分子关联构建可能的AMPK调节网络。进行了体外激酶测定，以初步验证12种新型AMPK靶点，这些靶点跨越各种细胞功能类别，包括转录、翻译、细胞迁移、蛋白质转运和能量稳态。在初步验证后，假设并实验测试了包括NAD合成酶1（NADSYN 1）和蛋白激酶B（AKT 2）的途径，以提供AMPK调节细胞迁移和维持分解代谢过程中细胞NAD+浓度的机制基础。这项研究描绘了一种方法，包括在硅片程序和体外实验，以产生可检验的假设AMPK调节细胞过程。本文的在线版本（doi：10.1186/s12918-015-0156-0）包含补充材料，可供授权用户使用。
AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine protein kinase that is activated by cellular perturbations associated with ATP depletion or stress. While AMPK modulates the activity of a variety of targets containing a specific phosphorylation consensus sequence, the number of AMPK targets and their influence over cellular processes is currently thought to be limited. We queried the human and the mouse proteomes for proteins containing AMPK phosphorylation consensus sequences. Integration of this database into Gaggle software facilitated the construction of probable AMPK-regulated networks based on known and predicted molecular associations. In vitro kinase assays were conducted for preliminary validation of 12 novel AMPK targets across a variety of cellular functional categories, including transcription, translation, cell migration, protein transport, and energy homeostasis. Following initial validation, pathways that include NAD synthetase 1 (NADSYN1) and protein kinase B (AKT2) were hypothesized and experimentally tested to provide a mechanistic basis for AMPK regulation of cell migration and maintenance of cellular NAD+ concentrations during catabolic processes. This study delineates an approach that encompasses both in silico procedures and in vitro experiments to produce testable hypotheses for AMPK regulation of cellular processes. The online version of this article (doi:10.1186/s12918-015-0156-0) contains supplementary material, which is available to authorized users.
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影响因子：
56.9
作者：
Hundley, HA;Walter, W;Craig, EA
通讯作者：
Craig, EA
DOI：
10.1073/pnas.0603730103
发表时间：
2006-09-05
影响因子：
11.1
作者：
Dixon, Jill;Jones, Natalie C.;Trainor, Paul A.
通讯作者：
Trainor, Paul A.
影响因子：
37.8
作者：
Dong Y;Zhang M;Liang B;Xie Z;Zhao Z;Asfa S;Choi HC;Zou MH
通讯作者：
Zou MH
影响因子：
3.9
作者：
Grundt, K;Skjeldal, L;Ostvold, AC
通讯作者：
Ostvold, AC
影响因子：
14.9
作者：
Avni, D;Biberman, Y;Meyuhas, O
通讯作者：
Meyuhas, O