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PERSPECTIVES IN PHARMACOLOGY
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina
Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), which are members of the mitogen-activated protein kinase superfamily, have been well characterized and are known to be involved in cell survival; however, recent evidence suggests that the activation of ERK1/2 also contributes to cell death in some cell types and organs under certain conditions. For example, ERK1/2 is activated in neuronal and renal epithelial cells upon exposure to oxidative stress and toxicants and deprivation of growth factors, and inhibition of the ERK pathway blocks apoptosis. ERK activation also occurs in animal models of ischemia- and trauma-induced brain injury and cisplatin-induced renal injury, and inactivation of ERK reduces the extent of tissue damage. In some studies, ERK has been implicated in apoptotic events upstream of mitochondrial cytochrome c release, whereas other studies have suggested the converse that ERK acts downstream of mitochondrial events and upstream of caspase-3 activation. ERK also can contribute to cell death through the suppression of the antiapoptotic signaling molecule Akt. Here we summarize the evidence and mechanism of ERK-induced apoptosis in both cell culture and in animal models.
Address correspondence to: Dr. Rick G. Schnellmann, Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun St., P. O. Box 250140, Charleston, SC 29425. E-mail: schnell{at}musc.edu
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