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cdc2–cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner

cdc2–cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner
cdc2–cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner
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.
cell cycle, elongation factor 2, mitosis, protein synthesis, translation
0261-4189
1005-1016
Smith, Ewan M.
738e731a-5867-426e-8345-dfa2727cca3e
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3
Smith, Ewan M.
738e731a-5867-426e-8345-dfa2727cca3e
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3

Smith, Ewan M. and Proud, Christopher G. (2008) cdc2–cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner. The EMBO Journal, 27 (7), 1005-1016. (doi:10.1038/emboj.2008.39).

Record type: Article

Abstract

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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More information

Published date: 13 March 2008
Keywords: cell cycle, elongation factor 2, mitosis, protein synthesis, translation
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 155587
URI: http://eprints.soton.ac.uk/id/eprint/155587
ISSN: 0261-4189
PURE UUID: 0c8273b5-f738-4d49-8ff6-447275aa91e3

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Date deposited: 28 May 2010 08:19
Last modified: 14 Mar 2024 01:39

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Contributors

Author: Ewan M. Smith
Author: Christopher G. Proud

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