Regulation of STAT3 by mu-opioid receptors in human neuroblastoma SH-SY5Y cells

Neuroreport. 2004 Jun 28;15(9):1431-5. doi: 10.1097/01.wnr.0000130433.90962.6e.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / enzymology
  • DNA-Binding Proteins / metabolism*
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroblastoma*
  • Pertussis Toxin / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Receptors, Opioid, mu / metabolism*
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism*
  • Tyrosine / metabolism
  • src-Family Kinases / metabolism

Substances

  • DNA-Binding Proteins
  • Receptors, Opioid, mu
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Tyrosine
  • Pertussis Toxin
  • Phosphatidylinositol 3-Kinases
  • src-Family Kinases
  • Proto-Oncogene Proteins c-raf
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase Kinases
  • MAP3K1 protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go