期刊
CELL METABOLISM
卷 22, 期 5, 页码 907-921出版社
CELL PRESS
DOI: 10.1016/j.cmet.2015.09.009
关键词
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资金
- CIRM [RB4-06087]
- NIH [R01 AG031198, T32 CA09302, R01 DK080425, P01 CA120964]
- NSF GRFP
- Robert M. and Anne T. Bass Stanford Graduate Fellowship
- Howard Hughes Medical Institute
- Biomedical Technology Research Centers program of the NIH National Institute of General Medical Sciences, NIH NIGMS [8P41GM103481]
- Thermo Scientifi LTQ-Orbitrap Velos [P41GM103481]
- Vincent Coates Foundation Mass Spectrometry Laboratory
- Stanford University Mass Spectrometry
AMP-activated protein kinase (AMPK) is a central energy gauge that regulates metabolism and has been increasingly involved in non-metabolic processes and diseases. However, AMPK's direct substrates in non-metabolic contexts are largely unknown. To better understand the AMPK network, we use a chemical genetics screen coupled to a peptide capture approach in whole cells, resulting in identification of direct AMPK phosphorylation sites. Interestingly, the high-confidence AMPK substrates contain many proteins involved in cell motility, adhesion, and invasion. AMPK phosphorylation of the RHOA guanine nucleotide exchange factor NET1A inhibits extracellular matrix degradation, an early step in cell invasion. The identification of direct AMPK phosphorylation sites also facilitates large-scale prediction of AMPK substrates. We provide an AMPK motif matrix and a pipeline to predict additional AMPK substrates from quantitative phosphoproteomics datasets. As AMPK is emerging as a critical node in aging and pathological processes, our study identifies potential targets for therapeutic strategies.
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