Mechanism of mitosis-specific activation of MEK1

Harding, A., Giles, N., Burgess, A., Hancock, J. F. and Gabrielli, B. G. (2003) Mechanism of mitosis-specific activation of MEK1. Journal of Biological Chemistry, 278 19: 16747-16754. doi:10.1074/jbc.M301015200

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Author Harding, A.
Giles, N.
Burgess, A.
Hancock, J. F.
Gabrielli, B. G.
Title Mechanism of mitosis-specific activation of MEK1
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2003-01-01
Year available 2003
Sub-type Article (original research)
DOI 10.1074/jbc.M301015200
Open Access Status File (Publisher version)
Volume 278
Issue 19
Start page 16747
End page 16754
Total pages 8
Editor H. Tabor
Place of publication Bethesda
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject C1
270103 Protein Targeting and Signal Transduction
730108 Cancer and related disorders
Abstract Activation of cyclin B-Cdc2 is an absolute requirement for entry into mitosis, but other protein kinase pathways that also have mitotic functions are activated during G(2)/M progression. The MAPK cascade has well established roles in entry and exit from mitosis in Xenopus, but relatively little is known about the regulation and function of this pathway in mammalian mitosis. Here we report a detailed analysis of the activity of all components of the Ras/Raf/MEK/ERK pathway in HeLa cells during normal G(2)/M. The focus of this pathway is the dramatic activation of an endomembrane-associated MEK1 without the corresponding activation of the MEK substrate ERK. This is because of the uncoupling of MEK1 activation from ERK activation. The mechanism of this uncoupling involves the cyclin B-Cdc2-dependent proteolytic cleavage of the N-terminal ERK-binding domain of MEK1 and the phosphorylation of Thr(286). These results demonstrate that cyclin B-Cdc2 activity regulates signaling through the MAPK pathway in mitosis.
Keyword Biochemistry & Molecular Biology
Xenopus Egg Extracts
Somatic-cell Mitosis
Phosphoinositide 3-kinase
G(2)/m Transition
Q-Index Code C1
Institutional Status UQ

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Created: Wed, 15 Aug 2007, 05:18:53 EST