Activation of the MAP kinase pathway by the protein kinase raf

Louise R. Howe, Sally J. Leevers, Néstor Gómez, Sara Nakielny, Philip Cohen, Christopher J. Marshall

    Research output: Contribution to journalArticle

    597 Citations (Scopus)

    Abstract

    Both MAP kinases and the protein kinase p74raf-1 are activated by many growth factors in a c-ras-dependent manner and by oncogenic p21ras. We were therefore interested in determining the relationship between MAP kinases and raf. The MAP kinase ERK2 is activated by expression of oncogenically activated raf, independently of cellular ras. Overexpressed p74raf-1 potentiates activation of ERK2 by EGF and TPA. MAP kinase kinase inactivated by phosphatase 2A treatment is phosphorylated and reactivated by incubation with p74raf-1 immunoprecipitated from phorbol estertreated cells. We conclude that raf protein kinase is upstream of MAP kinases and is either a MAP kinase kinase kinase or a MAP kinase kinase kinase kinase.

    Original languageEnglish
    Pages (from-to)335-342
    Number of pages8
    JournalCell
    Volume71
    Issue number2
    DOIs
    Publication statusPublished - 16 Oct 1992

    Fingerprint

    raf Kinases
    Protein Kinases
    MAP Kinase Kinase Kinases
    Phosphotransferases
    Chemical activation
    90-kDa Ribosomal Protein S6 Kinases
    Mitogen-Activated Protein Kinase Kinases
    Phosphoric Monoester Hydrolases
    Epidermal Growth Factor
    Intercellular Signaling Peptides and Proteins

    Cite this

    Howe, L. R., Leevers, S. J., Gómez, N., Nakielny, S., Cohen, P., & Marshall, C. J. (1992). Activation of the MAP kinase pathway by the protein kinase raf. Cell, 71(2), 335-342. https://doi.org/10.1016/0092-8674(92)90361-F
    Howe, Louise R. ; Leevers, Sally J. ; Gómez, Néstor ; Nakielny, Sara ; Cohen, Philip ; Marshall, Christopher J. / Activation of the MAP kinase pathway by the protein kinase raf. In: Cell. 1992 ; Vol. 71, No. 2. pp. 335-342.
    @article{b93e74c100cf4eb8b86dcb21b92712bb,
    title = "Activation of the MAP kinase pathway by the protein kinase raf",
    abstract = "Both MAP kinases and the protein kinase p74raf-1 are activated by many growth factors in a c-ras-dependent manner and by oncogenic p21ras. We were therefore interested in determining the relationship between MAP kinases and raf. The MAP kinase ERK2 is activated by expression of oncogenically activated raf, independently of cellular ras. Overexpressed p74raf-1 potentiates activation of ERK2 by EGF and TPA. MAP kinase kinase inactivated by phosphatase 2A treatment is phosphorylated and reactivated by incubation with p74raf-1 immunoprecipitated from phorbol estertreated cells. We conclude that raf protein kinase is upstream of MAP kinases and is either a MAP kinase kinase kinase or a MAP kinase kinase kinase kinase.",
    author = "Howe, {Louise R.} and Leevers, {Sally J.} and N{\'e}stor G{\'o}mez and Sara Nakielny and Philip Cohen and Marshall, {Christopher J.}",
    year = "1992",
    month = "10",
    day = "16",
    doi = "10.1016/0092-8674(92)90361-F",
    language = "English",
    volume = "71",
    pages = "335--342",
    journal = "Cell",
    issn = "0092-8674",
    publisher = "Elsevier",
    number = "2",

    }

    Howe, LR, Leevers, SJ, Gómez, N, Nakielny, S, Cohen, P & Marshall, CJ 1992, 'Activation of the MAP kinase pathway by the protein kinase raf', Cell, vol. 71, no. 2, pp. 335-342. https://doi.org/10.1016/0092-8674(92)90361-F

    Activation of the MAP kinase pathway by the protein kinase raf. / Howe, Louise R.; Leevers, Sally J.; Gómez, Néstor; Nakielny, Sara; Cohen, Philip; Marshall, Christopher J.

    In: Cell, Vol. 71, No. 2, 16.10.1992, p. 335-342.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Activation of the MAP kinase pathway by the protein kinase raf

    AU - Howe, Louise R.

    AU - Leevers, Sally J.

    AU - Gómez, Néstor

    AU - Nakielny, Sara

    AU - Cohen, Philip

    AU - Marshall, Christopher J.

    PY - 1992/10/16

    Y1 - 1992/10/16

    N2 - Both MAP kinases and the protein kinase p74raf-1 are activated by many growth factors in a c-ras-dependent manner and by oncogenic p21ras. We were therefore interested in determining the relationship between MAP kinases and raf. The MAP kinase ERK2 is activated by expression of oncogenically activated raf, independently of cellular ras. Overexpressed p74raf-1 potentiates activation of ERK2 by EGF and TPA. MAP kinase kinase inactivated by phosphatase 2A treatment is phosphorylated and reactivated by incubation with p74raf-1 immunoprecipitated from phorbol estertreated cells. We conclude that raf protein kinase is upstream of MAP kinases and is either a MAP kinase kinase kinase or a MAP kinase kinase kinase kinase.

    AB - Both MAP kinases and the protein kinase p74raf-1 are activated by many growth factors in a c-ras-dependent manner and by oncogenic p21ras. We were therefore interested in determining the relationship between MAP kinases and raf. The MAP kinase ERK2 is activated by expression of oncogenically activated raf, independently of cellular ras. Overexpressed p74raf-1 potentiates activation of ERK2 by EGF and TPA. MAP kinase kinase inactivated by phosphatase 2A treatment is phosphorylated and reactivated by incubation with p74raf-1 immunoprecipitated from phorbol estertreated cells. We conclude that raf protein kinase is upstream of MAP kinases and is either a MAP kinase kinase kinase or a MAP kinase kinase kinase kinase.

    UR - http://www.scopus.com/inward/record.url?scp=0026754369&partnerID=8YFLogxK

    U2 - 10.1016/0092-8674(92)90361-F

    DO - 10.1016/0092-8674(92)90361-F

    M3 - Article

    C2 - 1330321

    AN - SCOPUS:0026754369

    VL - 71

    SP - 335

    EP - 342

    JO - Cell

    JF - Cell

    SN - 0092-8674

    IS - 2

    ER -

    Howe LR, Leevers SJ, Gómez N, Nakielny S, Cohen P, Marshall CJ. Activation of the MAP kinase pathway by the protein kinase raf. Cell. 1992 Oct 16;71(2):335-342. https://doi.org/10.1016/0092-8674(92)90361-F