A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun

Simon Morton (Lead / Corresponding author), Roger J. Davis, Ann McLaren, Philip Cohen

    Research output: Contribution to journalArticle

    203 Citations (Scopus)

    Abstract

    We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNFα or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF-induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild-type mice and by ERK1/ERK2 alone in fibroblasts from JNK-deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA- or EGF-induced dephosphorylation of Thr239 in fibroblasts. The agonist-induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase.

    Original languageEnglish
    Pages (from-to)3876-3886
    Number of pages11
    JournalEMBO Journal
    Volume22
    Issue number15
    DOIs
    Publication statusPublished - 1 Aug 2003

    Fingerprint

    Phosphorylation
    Transcription Factors
    Fibroblasts
    Anisomycin
    Macrophages
    Epidermal Growth Factor
    Phospho-Specific Antibodies
    Phorbol Esters
    Phosphoric Monoester Hydrolases
    Protein Kinases
    Protein Isoforms
    Chemical activation

    Keywords

    • C-Jun
    • ERK
    • GSK3
    • JNK
    • LPS

    Cite this

    Morton, Simon ; Davis, Roger J. ; McLaren, Ann ; Cohen, Philip. / A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. In: EMBO Journal. 2003 ; Vol. 22, No. 15. pp. 3876-3886.
    @article{099fbbe4ac0b4e7aa4353b8a1a5d3eb0,
    title = "A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun",
    abstract = "We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNFα or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF-induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild-type mice and by ERK1/ERK2 alone in fibroblasts from JNK-deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA- or EGF-induced dephosphorylation of Thr239 in fibroblasts. The agonist-induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase.",
    keywords = "C-Jun, ERK, GSK3, JNK, LPS",
    author = "Simon Morton and Davis, {Roger J.} and Ann McLaren and Philip Cohen",
    year = "2003",
    month = "8",
    day = "1",
    doi = "10.1093/emboj/cdg388",
    language = "English",
    volume = "22",
    pages = "3876--3886",
    journal = "EMBO Journal",
    issn = "0261-4189",
    publisher = "EMBO Press",
    number = "15",

    }

    A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. / Morton, Simon (Lead / Corresponding author); Davis, Roger J.; McLaren, Ann; Cohen, Philip.

    In: EMBO Journal, Vol. 22, No. 15, 01.08.2003, p. 3876-3886.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun

    AU - Morton, Simon

    AU - Davis, Roger J.

    AU - McLaren, Ann

    AU - Cohen, Philip

    PY - 2003/8/1

    Y1 - 2003/8/1

    N2 - We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNFα or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF-induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild-type mice and by ERK1/ERK2 alone in fibroblasts from JNK-deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA- or EGF-induced dephosphorylation of Thr239 in fibroblasts. The agonist-induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase.

    AB - We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNFα or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF-induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild-type mice and by ERK1/ERK2 alone in fibroblasts from JNK-deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA- or EGF-induced dephosphorylation of Thr239 in fibroblasts. The agonist-induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase.

    KW - C-Jun

    KW - ERK

    KW - GSK3

    KW - JNK

    KW - LPS

    UR - http://www.scopus.com/inward/record.url?scp=0041524094&partnerID=8YFLogxK

    U2 - 10.1093/emboj/cdg388

    DO - 10.1093/emboj/cdg388

    M3 - Article

    VL - 22

    SP - 3876

    EP - 3886

    JO - EMBO Journal

    JF - EMBO Journal

    SN - 0261-4189

    IS - 15

    ER -