Regulation of STAT3 activity by G16-coupled receptors.
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.
Wu
Eddy H T
EH
Department of Biochemistry, The Molecular Neuroscience Center, and The Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Lo
Rico K H
RK
Wong
Yung H
YH
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D017930:Genes, Reporter; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000094942:Nociceptin Receptor
D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D011957:Receptors, Opioid; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D008156:Luciferases; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; C112631:G protein alpha 16; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human