TY - JOUR
T1 - Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons
AU - Trotter, Linda
AU - Panton, Wendy
AU - Hajimohamadreza, Iradj
AU - Petalidis, Lawrence
AU - Ward, Robin
AU - Fleming, Yvonne
AU - Armstrong, Christopher G.
AU - Cohen, Philip
AU - Karran, Eric H.
AU - Kinloch, Ross A.
PY - 2002/3/1
Y1 - 2002/3/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - c-Jun
KW - c-Jun N-terminal kinase
KW - Cerebellar granule neurons
KW - Mitogen-activated protein kinase kinase 4
KW - Mitogen-activated protein kinase kinase 7
KW - Stress-activated protein kinase
UR - http://www.scopus.com/inward/record.url?scp=0036498974&partnerID=8YFLogxK
U2 - 10.1016/S0304-3940(02)00005-8
DO - 10.1016/S0304-3940(02)00005-8
M3 - Article
C2 - 11849756
AN - SCOPUS:0036498974
SN - 0304-3940
VL - 320
SP - 29
EP - 32
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1-2
ER -