Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis

Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, i...

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Published in:	Science (American Association for the Advancement of Science) 1995-11, Vol.270 (5240), p.1326-1331
Main Authors:	Xia, Zhengui, Dickens, Martin, Raingeaud, Joël, Davis, Roger J., Greenberg, Michael E.
Format:	Article
Language:	eng
Subjects:	Ageing, cell death Alkaloids - pharmacology Anatomy Animals Antibodies Apoptosis Biological and medical sciences Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors Calcium-Calmodulin-Dependent Protein Kinases - genetics Calcium-Calmodulin-Dependent Protein Kinases - metabolism Cell death Cell Differentiation Cell growth Cell nucleus Cell physiology Cellular differentiation Cultured cells Enzyme Activation Fundamental and applied biological sciences. Psychology Genes Genes, jun Genetic vectors JNK Mitogen-Activated Protein Kinases Logical Thinking MAP Kinase Kinase 1 MAP Kinase Kinase 3 MAP Kinase Kinase 4 MAP Kinase Kinase Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular and cellular biology Nerve Growth Factors - pharmacology Neurology Neurons Neurons - cytology Neurons - enzymology p38 Mitogen-Activated Protein Kinases PC12 Cells Protein kinases Protein Kinases - metabolism Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Proteins Rats Research Article Rodents Signal Transduction Staurosporine Stimuli Sympathetic Nervous System - cytology T lymphocytes
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Summary:	Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH$_2$-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs. The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether a cell survives or undergoes apoptosis.
ISSN:	0036-8075 1095-9203