Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor

S. Traverse, N. Gomez, H. Paterson, C. Marshall, P. Cohen

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    Abstract

    Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min. declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but no nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus. where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.

    Original languageEnglish
    Pages (from-to)351-355
    Number of pages5
    JournalBiochemical Journal
    Volume288
    Issue number2
    DOIs
    Publication statusPublished - 1 Dec 1992

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    PC12 Cells
    Nerve Growth Factor
    Mitogen-Activated Protein Kinases
    Epidermal Growth Factor
    Mitogen-Activated Protein Kinase Kinases
    Chemical activation
    MAP Kinase Kinase 2
    Intercellular Signaling Peptides and Proteins
    MAP Kinase Kinase 1
    Protein Phosphatase 2
    Transcription
    Cytosol
    Catalytic Domain
    Genes

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    title = "Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor",
    abstract = "Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min. declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but no nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus. where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.",
    author = "S. Traverse and N. Gomez and H. Paterson and C. Marshall and P. Cohen",
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    T1 - Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor

    AU - Traverse, S.

    AU - Gomez, N.

    AU - Paterson, H.

    AU - Marshall, C.

    AU - Cohen, P.

    PY - 1992/12/1

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    N2 - Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min. declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but no nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus. where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.

    AB - Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min. declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but no nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus. where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.

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