Abstract
Heptahelical opioid receptors are implicated in the transcriptional regulation of neuronal development. Here we demonstrated that activation of mu-opioid receptors in human neuroblastoma SH-SY5Y cells led to the activation of signal transducer and activator of transcription 3 (STAT3), a transcription factor central to the regulation of numerous biological processes. The mu-opioid-induced activation of STAT3 is sensitive to receptor was further shown to pertussis toxin treatment and required JAK and Src tyrosine kinases, but not phosphatidylinositol 3-kinase. This mu-opioid-induced response was mediated via the extracellular signal-regulated protein kinase in a Raf-1-independent manner. The present study provides a foundation to explore the importance of STAT3 signaling in the regulation of neuronal growth and differentiation by the mu-opioid receptor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor / drug effects
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Cell Line, Tumor / enzymology
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DNA-Binding Proteins / metabolism*
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1*
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MAP Kinase Kinase Kinases / metabolism
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MAP Kinase Signaling System / physiology*
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Mitogen-Activated Protein Kinases / metabolism
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Neuroblastoma*
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Pertussis Toxin / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-raf / metabolism
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Receptors, Opioid, mu / metabolism*
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STAT3 Transcription Factor
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Trans-Activators / metabolism*
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Tyrosine / metabolism
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src-Family Kinases / metabolism
Substances
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DNA-Binding Proteins
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Receptors, Opioid, mu
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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Tyrosine
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases
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src-Family Kinases
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Proto-Oncogene Proteins c-raf
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 1
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MAP Kinase Kinase Kinases
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MAP3K1 protein, human
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GTP-Binding Protein alpha Subunits, Gi-Go