Identification of direct AMPK phosphorylation sites in cells reveals a role for AMPK in non-metabolic pathways

Placeholder Show Content

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
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2015
Issuance monographic
Language English

Creators/Contributors

Associated with Schaffer, Bethany Eleanor
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

Bibliographic information

Statement of responsibility Bethany Eleanor Schaffer.
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).

Also listed in

Loading usage metrics...