Identification of AMP-activated protein kinase targets by a consensus sequence search of the proteome

BMC Systems Biology

John Y-J Shyy²  Shu Chien¹  Shankar Subramaniam⁴  David A Johnson⁵  Lemar Smith⁵  Stephanie J King⁵  Marcy Martin²  Brendan Gongol³  Traci L Marin³ 

[1] Department of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego La Jolla 92093, CA, USA;Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla 92093, CA, USA;Department of Cardiopulmonary Sciences and Anatomy, Schools of Allied Health and Medicine, Loma Linda University, Loma Linda 92350, CA, USA;Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla 92093, CA, USA;Divisions of Biochemistry and Molecular Biology and Biomedical Sciences, University of California, Riverside 92521-0121, CA, USA

关键词: Network prediction;    Proteome;    Bioinformatics;    Phosphorylation consensus sequence;    NADSYN1;    FOXO3a;    MMP-2;    ATF2;    AKT2;    AMPK;   

Others  :  1159560
DOI  :  10.1186/s12918-015-0156-0

 received in 2014-08-20, accepted in 2015-02-24,  发布年份 2015

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2015 Marin et al.; licensee BioMed Central.

【 图 表 】

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