title: Discovery of new substrates of the elongation factor-2 kinase suggests a broader role in the cellular nutrient response.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Lazarus
authors.affiliation: Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Levin
authors.affiliation: 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.
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
mesh_terms: D000595:Amino Acid Sequence; D002477:Cells / Q000378:metabolism*; D019295:Computational Biology; D054736:Elongation Factor 2 Kinase / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D015203:Reproducibility of Results; D013379:Substrate Specificity
chemical_list: D010455:Peptides; C517689:EEF2K protein, human; D054736:Elongation Factor 2 Kinase
keywords: AMPK; Energy homeostasis; Translation elongation; alpha4; eEF2; eEF2K