Regulation of STAT3 activity by G16-coupled receptors

• Published in: Biochemical and biophysical research communications 2003-04, Vol.303 (3), p.920-925
• Main Authors: Wu, Eddy H T, Lo, Rico K H, Wong, Yung H
• Format: Article
• Language: English
• Subjects: Cell Line; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Genes, Reporter; GTP-Binding Protein alpha Subunits, Gq-G11; Heterotrimeric GTP-Binding Proteins - genetics; Heterotrimeric GTP-Binding Proteins - metabolism; Humans; Luciferases - genetics; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases - metabolism; 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; Signal Transduction; STAT3 Transcription Factor; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription, Genetic; Transfection
• ISSN: 0006-291X
• DOI: 10.1016/s0006-291x(03)00451-0

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.