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| Subject Categories: Signal Transduction | Proteins |
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| The EMBO Journal
(2008) 27, 1005–1016, doi:10.1038/emboj.2008.39 Published online 13 March 2008 |
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| cdc2–cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner |
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| Ewan M Smith1, 2 and Christopher G Proud1, 2 |
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1 Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, UK 2 Department of Biochemistry & Molecular Biology, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada To whom correspondence should be addressed Christopher G Proud, Department of Biochemistry & Molecular Biology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3. Tel.: +1 604 827 3923; Fax: +1 604 822 5227; E-mail: cgpr@interchange.ubc.ca Received 31 August 2007; Accepted 14 February 2008; Published online 13 March 2008. |
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| Abstract |
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| The calcium/calmodulin-dependent kinase that phosphorylates and inactivates eukaryotic elongation factor 2 (eEF2 kinase; eEF2K) is subject to multisite phosphorylation, which regulates its activity. Phosphorylation at Ser359 inhibits eEF2K activity even at high calcium concentrations. To identify the kinase that phosphorylates Ser359 in eEF2K, we developed an extensive purification protocol. Tryptic mass fingerprint analysis identified it as cdc2 (cyclin-dependent kinase 1). cdc2 co-purifies with Ser359 kinase activity and cdc2–cyclin B complexes phosphorylate eEF2K at Ser359. We demonstrate that cdc2 contributes to controlling eEF2 phosphorylation in cells. cdc2 is activated early in mitosis. Kinase activity against Ser359 in eEF2K also peaks at this stage of the cell cycle and eEF2 phosphorylation is low in mitotic cells. Inactivation of eEF2K by cdc2 may serve to keep eEF2 active during mitosis (where calcium levels rise) and thereby permit protein synthesis to proceed in mitotic cells. Amino-acid starvation decreases cdc2's activity against eEF2K, whereas loss of TSC2 (a negative regulator of mammalian target of rapamycin complex 1(mTORC1)) increases it. These data closely match the control of Ser359 phosphorylation and indicate that cdc2 may be regulated by mTORC1. |
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| Keywords: cell cycle, elongation factor 2, mitosis, protein synthesis, translation |
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