Project title: Regulation and Function of BDNF-activated ERK5 and ERK½ MAP Kinases in CNS Neurons
Completed in: 2007
Extracellular signal-regulated protein kinase (ERK) 1/2 pathway has been implicated in neuronal protection against several forms of neuronal apoptosis. However, the downstream mechanisms are not completely understood. Here we report that brain-derived neurotrophic factor (BDNF) protects embryonic cortical neurons from apoptosis after serum withdrawal. Furthermore, BDNF neuroprotection was mediated in part by activation of ERK1/2 signaling pathway. Importantly, we discovered that ERK1/2 activates ribosomal S6 kinase 2 (RSK2), which phosphorylates and activates myocyte enhancer factor 2C (MEF2C). We also provide evidence that RSK2/MEF2C are responsible for the neuroprotection afforded by ERK1/2. Together, our data identify ERK1/2-RSK2-MEF2C as a novel mechanism of neuroprotection.