Research

Stimulus-induced uncoupling of extracellular signal-regulated kinase phosphorylation from nuclear localization is dependent on docking domain interactions


Reference:

Caunt, C. J. and McArdle, C. A., 2010. Stimulus-induced uncoupling of extracellular signal-regulated kinase phosphorylation from nuclear localization is dependent on docking domain interactions. Journal of Cell Science, 123 (24), pp. 4310-4320.

Related documents:

[img]
Preview
PDF (Caunt_JCS_2010_123'_24_4310.pdf) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (9MB) | Preview

    Official URL:

    http://dx.doi.org/10.1242/jcs.076349

    Abstract

    Many stimuli activate the extracellular signal-regulated kinase (ERK) by phosphorylation on the TEY motif. Activated ERK characteristically accumulates in the nucleus, but the underlying mechanisms involved are unclear. Using automated microscopy to explore ERK regulation in single intact cells, we find that, when protein kinase C or epidermal growth factor receptors are activated, a substantial fraction of the ERK nuclear localization response is uncoupled from TEY phosphorylation. This phosphorylation-unattributable nuclear localization response occurs in the presence of inhibitors of tyrosine phosphatases and protein synthesis. It was also evident with a catalytically inactive ERK2-GFP mutant, and with a mutant incapable of binding the DEF (docking site for ERK, F/Y-X-F/Y-P) domains found in many ERK binding partners. It was, however, reduced by MEK inhibition and by mutations preventing either TEY phosphorylation or D (docking)-domain-dependent ERK binding (D319N). Thus, we show that MEK-catalysed ERK phosphorylation is necessary but not sufficient for the full nuclear localization response: there is an additional phosphorylation-unattributable component of the response that does not reflect induced expression of nuclear anchors and is independent of ERK catalytic activity or DEF-domain binding. It is, however, dependent upon D-domain binding, highlighting distinct roles of ERK motifs during nuclear targeting.

    Details

    Item Type Articles
    CreatorsCaunt, C. J.and McArdle, C. A.
    DOI10.1242/jcs.076349
    DepartmentsFaculty of Science > Biology & Biochemistry
    Publisher StatementCaunt_JCS_2010_123'_24_4310.pdf: The final published article is available from http://jcs.biologists.org
    RefereedNo
    StatusPublished
    ID Code22143

    Export

    Actions (login required)

    View Item

    Document Downloads

    More statistics for this item...