Content Loading...
Content Loading...
Product Reference
JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis.
| |
|
| Author |
Putcha, Girish V, et al. |
| Citation Information |
Neuron, 38: 899-914 (2003), : (2003) |
| Applications |
Kinase Assay |
| Related Products |
14-327, 36-004, 06-499, 14-301, 14-329 |
| Pub Med ID |
12818176 |
| |
|
Abstract
Trophic factor deprivation (TFD) activates c-Jun N-terminal kinases (JNKs), culminating in coordinate AP1-dependent transactivation of the BH3-only BCL-2 proteins BIM(EL) and HRK, which in turn are critical for BAX-dependent cytochrome c release, caspase activation, and apoptosis. Here, we report that TFD caused not only induction but also phosphorylation of BIM(EL). Mitochondrially localized JNKs but not upstream activators, like mixed-lineage kinases (MLKs) or mitogen-activated protein kinase kinases (MKKs), specifically phosphorylated BIM(EL) at Ser65, potentiating its proapoptotic activity. Inhibition of the JNK pathway attenuated BIM(EL) expression, prevented BIM(EL) phosphorylation, and abrogated TFD-induced apoptosis. Conversely, activation of this pathway promoted BIM(EL) expression and phosphorylation, causing BIM- and BAX-dependent cell death. Thus, JNKs regulate the proapoptotic activity of BIM(EL) during TFD, both transcriptionally and posttranslationally.
