%0 Journal Article
%T Identification of AMP-activated protein kinase targets by a consensus sequence search of the proteome.
%A Marin TL
%A Gongol B
%A Martin M
%A King SJ
%A Smith L
%A Johnson DA
%A Subramaniam S
%A Chien S
%A Shyy JY
%J BMC Syst Biol
%V 9
%N 0
%D Mar 2015 11
%M 25890336
暂无%R 10.1186/s12918-015-0156-0
%X <B>BACKGROUND: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.