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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 2/2008

01-06-2008

Dual-specificity MAP kinase phosphatases (MKPs) and cancer

Author: Stephen M. Keyse

Published in: Cancer and Metastasis Reviews | Issue 2/2008

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Abstract

There are ten mitogen-activated protein kinase (MAPK) phosphatases (MKPs) that act as negative regulators of MAPK activity in mammalian cells and these can be subdivided into three groups. The first comprises DUSP1/MKP-1, DUSP2/PAC1, DUSP4/MKP-2 and DUSP5/hVH-3, which are inducible nuclear phosphatases. With the exception of DUSP5, these MKPs display a rather broad specificity for inactivation of the ERK, p38 and JNK MAP kinases. The second group contains three closely related ERK-specific and cytoplasmic MKPs encoded by DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4. The final group consists of three MKPs DUSP8/hVH-5, DUSP10/MKP-5 and DUSP16/MKP-7 all of which preferentially inactivate the stress-activated p38 and JNK MAP kinases. Abnormal MAPK signalling will have important consequences for processes critical to the development and progression of human cancer. In addition, MAPK signalling also plays a key role in determining the response of tumour cells to conventional cancer therapies. The emerging roles of the dual-specificity MKPs in the regulation of MAPK activities in normal tissues has highlighted the possible pathophysiological consequences of either loss (or gain) of function of these enzymes as part of the oncogenic process. This review summarises the current evidence implicating the dual-specificity MKPs in the initiation and development of cancer and also on the outcome of treatment.
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Metadata
Title
Dual-specificity MAP kinase phosphatases (MKPs) and cancer
Author
Stephen M. Keyse
Publication date
01-06-2008
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 2/2008
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-008-9123-1

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