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Cell Signal. 2017 Jan;29:78-83. doi: 10.1016/j.cellsig.2016.10.006. Epub 2016 Oct 17.

Discovery of new substrates of the elongation factor-2 kinase suggests a broader role in the cellular nutrient response.

Author information

1
Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kevan.shokat@ucsf.edu.

Abstract

Elongation Factor-2 Kinase (eEF2K) in an unusual mammalian enzyme that has one known substrate, elongation factor-2. It belongs to a class of kinases, called alpha kinases, that has little sequence identity to the >500 conventional protein kinases, but performs the same reaction and has similar catalytic residues. The phosphorylation of eEF2 blocks translation elongation, which is thought to be critical to regulating cellular energy usage. Here we report a system for discovering new substrates of alpha kinases and identify the first new substrates of eEF2K including AMPK and alpha4, and determine a sequence motif for the kinase that shows a requirement for threonine residues as the target of phosphorylation. These new substrates suggest that eEF2K has a more diverse role in regulating cellular energy usage that involves multiple pathways and regulatory feedback.

KEYWORDS:

AMPK; Energy homeostasis; Translation elongation; alpha4; eEF2; eEF2K

PMID:
27760376
PMCID:
PMC5138099
DOI:
10.1016/j.cellsig.2016.10.006
[Indexed for MEDLINE]
Free PMC Article

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