Akt1 regulates a JNK scaffold during excitotoxic apoptosis.

Cell survival is determined by a balance among signaling cascades, including those that recruit the Akt and JNK pathways. Here we describe a novel interaction between Akt1 and JNK interacting protein 1 (JIP1), a JNK pathway scaffold. Direct association between Akt1 and JIP1 was observed in primary neurons. Neuronal exposure ...
to an excitotoxic stimulus decreased the Akt1-JIP1 interaction and concomitantly increased association between JIP1 and JNK. Akt1 interaction with JIP1 inhibited JIP1-mediated potentiation of JNK activity by decreasing JIP1 binding to specific JNK pathway kinases. Consistent with this view, neurons from Akt1-deficient mice exhibited higher susceptibility to kainate than wild-type littermates. Overexpression of Akt1 mutants that bind JIP1 reduced excitotoxic apoptosis. These results suggest that Akt1 binding to JIP1 acts as a regulatory gate preventing JNK activation, which is released under conditions of excitotoxic injury.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Arabidopsis Proteins, Carrier Proteins, Cell Survival, Cells, Cultured, Central Nervous System Diseases, Fetus, Gene Deletion, Gene Expression, Glutamic Acid, Hippocampus, Humans, JNK Mitogen-Activated Protein Kinases, Kainic Acid, Mice, Mice, Knockout, Mitogen-Activated Protein Kinases, Neurons, Neurotoxins, Plant Proteins, Potassium Channels, Protein Binding, Rats, Rats, Sprague-Dawley, Receptors, Glutamate, Signal Transduction
Neuron
Date: Aug. 15, 2002
Download Curated Data For This Publication
5619
Switch View:
  • Interactions 1