Dual-specificity MAP kinase phosphatases (MKPs) and cancer

    Research output: Contribution to journalReview article

    297 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)253-261
    Number of pages9
    JournalCancer and Metastasis Reviews
    Volume27
    Issue number2
    DOIs
    Publication statusPublished - Jun 2008

    Keywords

    • MAP kinase
    • DUSP
    • MAP kinase phosphatase
    • cancer
    • ACTIVATED PROTEIN-KINASE
    • SIGNAL-REGULATED KINASE
    • INNATE IMMUNE-RESPONSES
    • CELL LUNG-CANCER
    • PANCREATIC-CANCER
    • GENE-EXPRESSION
    • TUMOR SUPPRESSION
    • PHYSIOLOGICAL FUNCTIONS
    • OVARIAN-CARCINOMA
    • ACUTE-LEUKEMIA

    Cite this

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    title = "Dual-specificity MAP kinase phosphatases (MKPs) and cancer",
    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, ACTIVATED PROTEIN-KINASE, SIGNAL-REGULATED KINASE, INNATE IMMUNE-RESPONSES, CELL LUNG-CANCER, PANCREATIC-CANCER, GENE-EXPRESSION, TUMOR SUPPRESSION, PHYSIOLOGICAL FUNCTIONS, OVARIAN-CARCINOMA, ACUTE-LEUKEMIA",
    author = "Keyse, {Stephen M.}",
    year = "2008",
    month = "6",
    doi = "10.1007/s10555-008-9123-1",
    language = "English",
    volume = "27",
    pages = "253--261",
    journal = "Cancer and Metastasis Reviews",
    issn = "0167-7659",
    publisher = "Springer Verlag",
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    }

    Dual-specificity MAP kinase phosphatases (MKPs) and cancer. / Keyse, Stephen M.

    In: Cancer and Metastasis Reviews, Vol. 27, No. 2, 06.2008, p. 253-261.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - Dual-specificity MAP kinase phosphatases (MKPs) and cancer

    AU - Keyse, Stephen M.

    PY - 2008/6

    Y1 - 2008/6

    N2 - 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.

    AB - 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.

    KW - MAP kinase

    KW - DUSP

    KW - MAP kinase phosphatase

    KW - cancer

    KW - ACTIVATED PROTEIN-KINASE

    KW - SIGNAL-REGULATED KINASE

    KW - INNATE IMMUNE-RESPONSES

    KW - CELL LUNG-CANCER

    KW - PANCREATIC-CANCER

    KW - GENE-EXPRESSION

    KW - TUMOR SUPPRESSION

    KW - PHYSIOLOGICAL FUNCTIONS

    KW - OVARIAN-CARCINOMA

    KW - ACUTE-LEUKEMIA

    U2 - 10.1007/s10555-008-9123-1

    DO - 10.1007/s10555-008-9123-1

    M3 - Review article

    VL - 27

    SP - 253

    EP - 261

    JO - Cancer and Metastasis Reviews

    JF - Cancer and Metastasis Reviews

    SN - 0167-7659

    IS - 2

    ER -