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

Overview

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.

authors

  • Schaffer, Bethany Eleanor
  • Levin, Rebecca S
  • Hertz, Nicholas T
  • Maures, Travis J
  • Schoof, Michael L
  • Hollstein, Pablo E
  • Benayoun, Bérénice A
  • Banko, Max R
  • Shaw, Reuben J
  • Shokat, Kevan M
  • Brunet, Anne

publication date

  • October 8, 2015

Research

keywords

  • AMP-Activated Protein Kinases
  • Cell Adhesion
  • Oncogene Proteins
  • Protein Interaction Maps

Identity

PubMed Central ID

  • PMC4635044

Scopus Document Identifier

  • 84948425160

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2015.09.009

PubMed ID

  • 26456332

Additional Document Info

volume

  • 22

issue

  • 5