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https://hdl.handle.net/2440/86400
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Type: | Journal article |
Title: | Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains |
Author: | Pigott, C. Mikolajek, H. Moore, C. Finn, S. Phippen, C. Werner, J. Proud, C. |
Citation: | Biochemical Journal, 2012; 442(1):105-118 |
Publisher: | Portland Press |
Issue Date: | 2012 |
ISSN: | 0264-6021 1470-8728 |
Statement of Responsibility: | Craig R. Pigott, Halina Mikolajek, Claire E. Moore, Stephen J. Finn, Curtis W. Phippen, Jörn M. Werner, and Christopher G. Proud |
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. |
Keywords: | Calmodulin (CaM); eukaryotic elongation factor 2 (eEF2); α-kinase; SEL1 domain |
Rights: | © 2012 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1042/BJ20111536 |
Published version: | http://dx.doi.org/10.1042/bj20111536 |
Appears in Collections: | Aurora harvest 7 Molecular and Biomedical Science publications |
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hdl_86400.pdf | Published version | 1.12 MB | Adobe PDF | View/Open |
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