Dualspecificity MAP kinase phosphatases MKPs an

Authors: Stephen M Keyse

Publish Date: 2008/03/11

Volume: 27, Issue: 2, Pages: 253-261

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Abstract

There are ten mitogenactivated 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/MKP1 DUSP2/PAC1 DUSP4/MKP2 and DUSP5/hVH3 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 ERKspecific and cytoplasmic MKPs encoded by DUSP6/MKP3 DUSP7/MKPX and DUSP9/MKP4 The final group consists of three MKPs DUSP8/hVH5 DUSP10/MKP5 and DUSP16/MKP7 all of which preferentially inactivate the stressactivated 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 dualspecificity 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 dualspecificity MKPs in the initiation and development of cancer and also on the outcome of treatment

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