Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons

Linda Trotter, Wendy Panton, Iradj Hajimohamadreza, Lawrence Petalidis, Robin Ward, Yvonne Fleming, Christopher G. Armstrong, Philip Cohen, Eric H. Karran, Ross A. Kinloch (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    A stress-activated protein kinase pathway comprising mitogen-activated protein kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor c-Jun is implicated in neuronal apoptosis. Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN). MKK7, but not MKK4, was activated within the first 4-6 h in four independent sets of 14-h CGN apoptosis time-courses. CEP-1347 (500 nM), an mixed-lineage kinase 3 inhibitor, prevented MKK7 activation and cell death following exposure of CGN cultures to LK-induced apoptosis. Western blot analysis revealed that levels of phosphorylated c-Jun were elevated between 30 min and 10 h of CGN apoptosis, temporally consistent with MKK7 activation. These data suggest that MKK7 is responsible for activating the JNK pathway during LK-induced CGN apoptosis.

    Original languageEnglish
    Pages (from-to)29-32
    Number of pages4
    JournalNeuroscience Letters
    Volume320
    Issue number1-2
    DOIs
    Publication statusPublished - 1 Mar 2002

    Keywords

    • Apoptosis
    • c-Jun
    • c-Jun N-terminal kinase
    • Cerebellar granule neurons
    • Mitogen-activated protein kinase kinase 4
    • Mitogen-activated protein kinase kinase 7
    • Stress-activated protein kinase

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