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Differential effects of stress stimuli on a JNK-inactivating phosphatase

Oncogene volume 21, pages 2387–2397 (2002)Cite this article

Abstract

Stress signals elicit a wide variety of cellular responses, many of which converge on the phosphorylation of JNK and p38 kinases, the activation of which has been well-characterized. How these kinases are switched off by dephosphorylation is not well understood. Here we describe how diverse cellular stresses affect differently the stability and activity of a JNK-inactivating dual-specificity threonine-tyrosine phosphatase M3/6. Both anisomycin and arsenite activate the JNK pathway and, in addition, inactivate the M3/6 phosphatase. However, while anisomycin treatment of cells leads to M3/6 protein degradation, arsenite appears to inactivate M3/6 directly. These results might have implications for the mechanism of tumour promotion by arsenic.

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Abbreviations

HEK293 cells:

human embryonic kidney 293 cells

JNK:

c-Jun N-terminal kinase

SAPK:

stress-activated protein kinase

ERK:

extracellular signal-regulated kinase

SEK1:

SAPK/ERK kinase 1

DMSO:

dimethyl sulphoxide

FCS:

foetal calf serum

GST:

glutathione S-transferase

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Acknowledgements

This work was funded by the Cancer Research Campaign and Breakthrough Breast Cancer. We thank CJ Marshall, M Olson and M Coleman for helpful suggestions, reagents and discussions.

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  1. Aspasia Theodosiou

    Present address: Biomedical Science Research Centre “Alexander Fleming”, PO BOX 74145, Varkiza 166-02, Athens, Greece

Authors and Affiliations

  1. CRC Gene Function and Regulation Group, The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK

    Aspasia Theodosiou & Alan Ashworth

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  2. Alan Ashworth
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Correspondence to Alan Ashworth.

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Theodosiou, A., Ashworth, A. Differential effects of stress stimuli on a JNK-inactivating phosphatase. Oncogene 21, 2387–2397 (2002). https://doi.org/10.1038/sj.onc.1205309

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