Regulation of STAT3 activity by G16-coupled receptors

Biochem Biophys Res Commun. 2003 Apr 11;303(3):920-5. doi: 10.1016/s0006-291x(03)00451-0.

Abstract

A number of G protein-coupled receptors (GPCRs) have been shown to stimulate signal transducers and activators of transcription (STAT) activities while STAT3 activation by G alpha(o) can lead to neoplastic transformation in fibroblasts. In the present study we examined the ability of GPCRs to activate STAT3 via G alpha(16), a G alpha subunit which is primarily expressed in hematopoietic cells. In HEK 293 cells expressing a STAT3-driven luciferase reporter, the G alpha(16)-coupled ORL(1) and fMLP receptors stimulated luciferase activity upon activation by their agonists. Agonist-induced STAT3 activity required coexpression of G alpha(16) and was resistant to PTX treatment. Upon activation of the ORL(1) and fMLP receptors, phosphorylation of STAT3 at Tyr(705) was detected by immunoblot analysis. Additional experiments indicated that GPCR-mediated STAT3 activation was dependent on JAK and Raf1 signaling, but did not require phosphatidylinositol 3-kinase. This is the first study that demonstrates the stimulatory effect of ORL(1) and fMLP receptors on STAT3 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Genes, Reporter
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Luciferases / genetics
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases / metabolism
  • Nociceptin Receptor
  • Pertussis Toxin / pharmacology
  • Phosphorylation
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / metabolism
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism
  • Receptors, Peptide / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription, Genetic
  • Transfection

Substances

  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Opioid
  • Receptors, Peptide
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Luciferases
  • Pertussis Toxin
  • Mitogen-Activated Protein Kinases
  • G protein alpha 16
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins
  • Nociceptin Receptor
  • OPRL1 protein, human