Abstract
We examined the effect of insulin on the expression of the activity-regulated cytoskeleton-associated gene (ARC), an effector immediate early gene with a proposed role in memory formation. In human SH-SY5Y neuroblastoma cells, application of insulin leads to dramatic increase in ARC mRNA and protein levels. Inhibition experiments reveal, that p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and tyrosine kinase (src) activity are required for the insulin-induced ARC expression in SH-SY5Y cells, whereas protein kinase C is not involved in the signal transduction pathway. Our data indicated for the first time a correlation of the insulin-controlled signal cascade and the induction of synaptic plasticity-associated immediate early genes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Central Nervous System / enzymology
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Central Nervous System / growth & development
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Cytoskeletal Proteins / drug effects
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Cytoskeletal Proteins / genetics*
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Cytoskeletal Proteins / metabolism
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Developmental / physiology
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Humans
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Insulin / metabolism*
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Insulin / pharmacology
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Memory / physiology
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Mitogen-Activated Protein Kinases / metabolism*
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Neuroblastoma
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Neuronal Plasticity / genetics
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Neurons / drug effects
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Neurons / enzymology*
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Protein Kinase C / metabolism*
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Proto-Oncogene Proteins p21(ras) / metabolism*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Signal Transduction / genetics
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Synapses / metabolism
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Transcription, Genetic / drug effects
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Transcription, Genetic / physiology
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Tumor Cells, Cultured
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src-Family Kinases / metabolism*
Substances
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Cytoskeletal Proteins
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Enzyme Inhibitors
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Insulin
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Nerve Tissue Proteins
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RNA, Messenger
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activity regulated cytoskeletal-associated protein
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src-Family Kinases
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Protein Kinase C
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Mitogen-Activated Protein Kinases
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)