Identification of direct AMPK phosphorylation sites in cells reveals a role for AMPK in non-metabolic pathways
Abstract/Contents
- 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.
Description
Type of resource | text |
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Form | electronic; electronic resource; remote |
Extent | 1 online resource. |
Publication date | 2015 |
Issuance | monographic |
Language | English |
Creators/Contributors
Associated with | Schaffer, Bethany Eleanor | |
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Associated with | Stanford University, Cancer Biology Program. | |
Primary advisor | Brunet, Anne, 1972- | |
Thesis advisor | Brunet, Anne, 1972- | |
Thesis advisor | Elias, Joshua | |
Thesis advisor | Ferrell, James Ellsworth | |
Thesis advisor | Snyder, Michael, Ph. D | |
Thesis advisor | Winslow, Monte | |
Advisor | Elias, Joshua | |
Advisor | Ferrell, James Ellsworth | |
Advisor | Snyder, Michael, Ph. D | |
Advisor | Winslow, Monte |
Subjects
Genre | Theses |
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Bibliographic information
Statement of responsibility | Bethany Eleanor Schaffer. |
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Note | Submitted to the Program in Cancer Biology. |
Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Bethany Eleanor Schaffer
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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