Proteomics

Dataset Information

85

Identification of AMPK phosphorylation sites reveals a network of proteins involved in cell invasion and facilitates large-scale substrate prediction


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo sapiens  

TISSUE(S): Cell Culture

DISEASE(S): Not Available

SUBMITTER: Rebecca Levin  

LAB HEAD: Kevan M. Shokat

PROVIDER: PXD003019 | Pride | 2015-10-09

REPOSITORIES: Pride

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Publications

Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction.

Schaffer Bethany E BE   Levin Rebecca S RS   Hertz Nicholas T NT   Maures Travis J TJ   Schoof Michael L ML   Hollstein Pablo E PE   Benayoun Bérénice A BA   Banko Max R MR   Shaw Reuben J RJ   Shokat Kevan M KM   Brunet Anne A  

Cell metabolism 20151008 5


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 man  ...[more]

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