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Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains

Pigott, Craig R., Mikolajek, Halina, Moore, Claire E., Finn, Stephen J., Phippen, Curtis W., Werner, Jörn M., Proud, Christopher G.·2012·Biochemical Journal
DOI 10.1042/bj20111536PMC PMC3268225
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Abstract

eEF2K (eukaryotic elongation factor 2 kinase) is a Ca2+/CaM (calmodulin)-dependent protein kinase which regulates the translation elongation machinery. eEF2K belongs to the small group of so-called ‘α-kinases’ which are distinct from the main eukaryotic protein kinase superfamily. In addition to the α-kinase catalytic domain, other domains have been identified in eEF2K: a CaM-binding region, N-terminal to the kinase domain; a C-terminal region containing several predicted α-helices (resembling SEL1 domains); and a probably rather unstructured ‘linker’ region connecting them. In the present paper, we demonstrate: (i) that several highly conserved residues, implicated in binding ATP or metal ions, are critical for eEF2K activity; (ii) that Ca2+/CaM enhance the ability of eEF2K to bind to ATP, providing the first insight into the allosteric control of eEF2K; (iii) that the CaM-binding/α-kinase domain of eEF2K itself possesses autokinase activity, but is unable to phosphorylate substrates in trans; (iv) that phosphorylation of these substrates requires the SEL1-like domains of eEF2K; and (v) that highly conserved residues in the C-terminal tip of eEF2K are essential for the phosphorylation of eEF2, but not a peptide substrate. On the basis of these findings, we propose a model for the functional organization and control of eEF2K.

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  • eef2k encodes a calcium/calmodulin-dependent protein kinase, which phosphorylates eukaryotic elongation factor 2 (eEF2) to inhibit translational elongation.

    “The eef2k encodes a calcium/calmodulin-dependent protein kinase, which phosphorylates eukaryotic elongation factor 2 (eEF2) to inhibit translational elongation34,35.”

    From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [34]

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Authors
Pigott, C. R., Mikolajek, H., Moore, C. E., Finn, S. J., Phippen, C. W., Werner, J. M., & Proud, C. G.
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2012-01-27
Volume
442
Issue
1
Pages
105-118
ISSN
  • 0264-6021
  • 1470-8728
DOI
10.1042/bj20111536
PMC
PMC3268225
Cited by
43
References
2
Language
en
Licence
creativecommons.org/licenses/by-nc/2.5/ (vor, 2736 d)

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