Cancer and Metastasis Reviews

, Volume 27, Issue 2, pp 253–261

Dual-specificity MAP kinase phosphatases (MKPs) and cancer

Article

DOI: 10.1007/s10555-008-9123-1

Cite this article as:
Keyse, S.M. Cancer Metastasis Rev (2008) 27: 253. doi:10.1007/s10555-008-9123-1

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.

Keywords

MAP kinase DUSP MAP kinase phosphatase Cancer 

Abbreviations

ALL

acute lymphocytic leukaemia

AML

acute myeloid leukaemia

BM

bone marrow

DUSP

dual-specificity protein phosphatase

ERK

extracellular-signal regulated kinase

JNK

c-Jun amino-terminal kinase

MAPK

mitogen-activated protein kinase

MEF

mouse embryo fibroblast

MKK or MEK

MAPK kinase

MKKK or MEKK

MAPK kinase kinase

MKP

MAP kinase phosphatase

NSCLC

non-small cell lung cancer

SCA

serous ovarian carcinoma

SAGE

serial analysis of gene expression

SBT

serous borderline ovarian tumour

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Cancer Research UK Stress Response Laboratory, Biomedical Research Centre, Level 5Ninewells Hospital and Medical SchoolDundeeUK

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