Truncated MEK1 is required for transient activation of MAPK signalling in G2 phase cells

Pike, Tanya, Widberg, Charlotte, Goodall, Andrew, Payne, Elizabeth, Giles, Nichole, Hancock, John and Gabrielli, Brian (2013) Truncated MEK1 is required for transient activation of MAPK signalling in G2 phase cells. Cellular Signalling, 25 6: 1423-1428. doi:10.1016/j.cellsig.2013.03.014

Author Pike, Tanya
Widberg, Charlotte
Goodall, Andrew
Payne, Elizabeth
Giles, Nichole
Hancock, John
Gabrielli, Brian
Title Truncated MEK1 is required for transient activation of MAPK signalling in G2 phase cells
Journal name Cellular Signalling   Check publisher's open access policy
ISSN 0898-6568
Publication date 2013-06-01
Sub-type Article (original research)
DOI 10.1016/j.cellsig.2013.03.014
Open Access Status Not Open Access
Volume 25
Issue 6
Start page 1423
End page 1428
Total pages 6
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract The primary endpoint of signalling through the canonical Raf-MEK-ERK MAP kinase cascade is ERK activation. Here we report a novel signalling outcome for this pathway. Activation of the MAP kinase pathway by growth factors or phorbol esters during G2 phase results in only transient activations of ERK and p90RSK, then suppression to below control levels. A small peak of ERK and p90RSK activation in early G2 phase cells was identified, and inhibition of this delayed entry into mitosis. The previously identified, proteolytically cleaved form of MEK1 termed tMEK (truncated MEK1), is also induced with G2 phase MAPK pathway activation. We demonstrate that addition of recombinant mutants of MEK1 with an N-terminal truncation similar to that of tMEK also inhibited ERK and p90RSK activations and delayed progression into mitosis. Only catalytically inactive forms of tMEK were capable of these effects, but surprisingly, phosphorylation on the activating Ser218/222 sites was also required. A lack of MEK1 or ability to accumulate tMEK resulted in the absence of the feedback inhibition of ERK and p90RSK activations. tMEK is a novel output from the canonical MAP kinase signalling pathway, acting in a MAPK signalling-regulated dominant negative manner to inhibit ERK and p90RSK activations, acting as a dampening mechanism to reduce the magnitude or duration of MAPK pathway signalling in G2/M phase.
Keyword MAPK
G2 phase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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