Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase

L A Groom, A A Sneddon, D R Alessi, S Dowd, S M Keyse

    Research output: Contribution to journalArticle

    351 Citations (Scopus)

    Abstract

    The Pyst1 and Pyst2 mRNAs encode closely related proteins, which are novel members of a family of dual-specificity MAP kinase phosphatases typified by CL100/MKP-1. Pyst1 is expressed constitutively in human skin fibroblasts and, in contrast to other members of this family of enzymes, its mRNA is not inducible by either stress or mitogens. Furthermore, unlike the nuclear CL100 protein, Pyst1 is localized in the cytoplasm of transfected Cos-1 cells. Like CL100/ MKP-1, Pyst1 dephosphorylates and inactivates MAP kinase in vitro and in vivo. In addition, Pyst1 is able to form a physical complex with endogenous MAP kinase in Cos-1 cells. However, unlike CL100, Pyst1 displays very low activity towards the stress-activated protein kinases (SAPKs) or RK/p38 in vitro, indicating that these kinases are not physiological substrates for Pyst1. This specificity is underlined by the inability of Pyst1 to block either the stress-mediated activation of the JNK-1 SAP kinase or RK/p38 in vivo, or to inhibit nuclear signalling events mediated by the SAP kinases in response to UV radiation. Our results provide the first evidence that the members of the MAP kinase family of enzymes are differentially regulated by dual-specificity phosphatases and also indicate that the MAP kinases may be regulated by different members of this family of enzymes depending on their subcellular location.
    Original languageEnglish
    Pages (from-to)3621-32
    Number of pages12
    JournalEMBO Journal
    Volume15
    Issue number14
    Publication statusPublished - 1996

    Fingerprint

    Dual-Specificity Phosphatases
    Phosphotransferases
    Enzymes
    Dual Specificity Phosphatase 1
    Mitogen-Activated Protein Kinase 8
    Messenger RNA
    Fibroblasts
    Nuclear Proteins
    Heat-Shock Proteins
    Mitogens
    Ultraviolet radiation
    Protein Kinases
    Skin
    Cytoplasm
    Chemical activation
    Radiation
    Substrates

    Keywords

    • 3T3 Cells
    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • Calcium-Calmodulin-Dependent Protein Kinases
    • Cell Cycle Proteins
    • Cell Line, Transformed
    • Cell Nucleus
    • Cells, Cultured
    • Cercopithecus aethiops
    • DNA Primers
    • Dual Specificity Phosphatase 1
    • Dual Specificity Phosphatase 6
    • Fibroblasts
    • Humans
    • Immediate-Early Proteins
    • JNK Mitogen-Activated Protein Kinases
    • Mice
    • Mitogen-Activated Protein Kinase 1
    • Mitogen-Activated Protein Kinases
    • Molecular Sequence Data
    • Phosphoprotein Phosphatases
    • Protein Phosphatase 1
    • Protein Tyrosine Phosphatases
    • Protein-Tyrosine Kinases
    • RNA, Messenger
    • Rabbits
    • Rats
    • Sequence Homology, Amino Acid
    • Signal Transduction
    • Skin
    • Ultraviolet Rays
    • Xenopus
    • p38 Mitogen-Activated Protein Kinases

    Cite this

    Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. / Groom, L A; Sneddon, A A; Alessi, D R; Dowd, S; Keyse, S M.

    In: EMBO Journal, Vol. 15, No. 14, 1996, p. 3621-32.

    Research output: Contribution to journalArticle

    Groom, L A ; Sneddon, A A ; Alessi, D R ; Dowd, S ; Keyse, S M. / Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. In: EMBO Journal. 1996 ; Vol. 15, No. 14. pp. 3621-32.
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    abstract = "The Pyst1 and Pyst2 mRNAs encode closely related proteins, which are novel members of a family of dual-specificity MAP kinase phosphatases typified by CL100/MKP-1. Pyst1 is expressed constitutively in human skin fibroblasts and, in contrast to other members of this family of enzymes, its mRNA is not inducible by either stress or mitogens. Furthermore, unlike the nuclear CL100 protein, Pyst1 is localized in the cytoplasm of transfected Cos-1 cells. Like CL100/ MKP-1, Pyst1 dephosphorylates and inactivates MAP kinase in vitro and in vivo. In addition, Pyst1 is able to form a physical complex with endogenous MAP kinase in Cos-1 cells. However, unlike CL100, Pyst1 displays very low activity towards the stress-activated protein kinases (SAPKs) or RK/p38 in vitro, indicating that these kinases are not physiological substrates for Pyst1. This specificity is underlined by the inability of Pyst1 to block either the stress-mediated activation of the JNK-1 SAP kinase or RK/p38 in vivo, or to inhibit nuclear signalling events mediated by the SAP kinases in response to UV radiation. Our results provide the first evidence that the members of the MAP kinase family of enzymes are differentially regulated by dual-specificity phosphatases and also indicate that the MAP kinases may be regulated by different members of this family of enzymes depending on their subcellular location.",
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    TY - JOUR

    T1 - Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase

    AU - Groom, L A

    AU - Sneddon, A A

    AU - Alessi, D R

    AU - Dowd, S

    AU - Keyse, S M

    PY - 1996

    Y1 - 1996

    N2 - The Pyst1 and Pyst2 mRNAs encode closely related proteins, which are novel members of a family of dual-specificity MAP kinase phosphatases typified by CL100/MKP-1. Pyst1 is expressed constitutively in human skin fibroblasts and, in contrast to other members of this family of enzymes, its mRNA is not inducible by either stress or mitogens. Furthermore, unlike the nuclear CL100 protein, Pyst1 is localized in the cytoplasm of transfected Cos-1 cells. Like CL100/ MKP-1, Pyst1 dephosphorylates and inactivates MAP kinase in vitro and in vivo. In addition, Pyst1 is able to form a physical complex with endogenous MAP kinase in Cos-1 cells. However, unlike CL100, Pyst1 displays very low activity towards the stress-activated protein kinases (SAPKs) or RK/p38 in vitro, indicating that these kinases are not physiological substrates for Pyst1. This specificity is underlined by the inability of Pyst1 to block either the stress-mediated activation of the JNK-1 SAP kinase or RK/p38 in vivo, or to inhibit nuclear signalling events mediated by the SAP kinases in response to UV radiation. Our results provide the first evidence that the members of the MAP kinase family of enzymes are differentially regulated by dual-specificity phosphatases and also indicate that the MAP kinases may be regulated by different members of this family of enzymes depending on their subcellular location.

    AB - The Pyst1 and Pyst2 mRNAs encode closely related proteins, which are novel members of a family of dual-specificity MAP kinase phosphatases typified by CL100/MKP-1. Pyst1 is expressed constitutively in human skin fibroblasts and, in contrast to other members of this family of enzymes, its mRNA is not inducible by either stress or mitogens. Furthermore, unlike the nuclear CL100 protein, Pyst1 is localized in the cytoplasm of transfected Cos-1 cells. Like CL100/ MKP-1, Pyst1 dephosphorylates and inactivates MAP kinase in vitro and in vivo. In addition, Pyst1 is able to form a physical complex with endogenous MAP kinase in Cos-1 cells. However, unlike CL100, Pyst1 displays very low activity towards the stress-activated protein kinases (SAPKs) or RK/p38 in vitro, indicating that these kinases are not physiological substrates for Pyst1. This specificity is underlined by the inability of Pyst1 to block either the stress-mediated activation of the JNK-1 SAP kinase or RK/p38 in vivo, or to inhibit nuclear signalling events mediated by the SAP kinases in response to UV radiation. Our results provide the first evidence that the members of the MAP kinase family of enzymes are differentially regulated by dual-specificity phosphatases and also indicate that the MAP kinases may be regulated by different members of this family of enzymes depending on their subcellular location.

    KW - 3T3 Cells

    KW - Amino Acid Sequence

    KW - Animals

    KW - Base Sequence

    KW - Calcium-Calmodulin-Dependent Protein Kinases

    KW - Cell Cycle Proteins

    KW - Cell Line, Transformed

    KW - Cell Nucleus

    KW - Cells, Cultured

    KW - Cercopithecus aethiops

    KW - DNA Primers

    KW - Dual Specificity Phosphatase 1

    KW - Dual Specificity Phosphatase 6

    KW - Fibroblasts

    KW - Humans

    KW - Immediate-Early Proteins

    KW - JNK Mitogen-Activated Protein Kinases

    KW - Mice

    KW - Mitogen-Activated Protein Kinase 1

    KW - Mitogen-Activated Protein Kinases

    KW - Molecular Sequence Data

    KW - Phosphoprotein Phosphatases

    KW - Protein Phosphatase 1

    KW - Protein Tyrosine Phosphatases

    KW - Protein-Tyrosine Kinases

    KW - RNA, Messenger

    KW - Rabbits

    KW - Rats

    KW - Sequence Homology, Amino Acid

    KW - Signal Transduction

    KW - Skin

    KW - Ultraviolet Rays

    KW - Xenopus

    KW - p38 Mitogen-Activated Protein Kinases

    M3 - Article

    VL - 15

    SP - 3621

    EP - 3632

    JO - EMBO Journal

    JF - EMBO Journal

    SN - 0261-4189

    IS - 14

    ER -