Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction.
Interleukin-6 (IL-6) induces tyrosine phosphorylation and activation of the latent transcription factor Stat3 in HepG2 cells. Mutation of Stat3 tyrosine 705 to phenylalanine (Y705F) inhibits IL-6-induced tyrosine phosphorylation of this Stat3 mutant in transfected HepG2 cells. In cotransfections of HepG2 cells, the Stat3 mutant Y705F causes a reduction of the tyrosine phosphorylation of wild type Stat3-FLAG. Moreover, Y705F inhibits the action of endogenous Stat3 in cotransfected cells, reducing IL-6 induction of a Stat3-responsive reporter construct. Y705F therefore acts as a dominant negative mutation of Stat3.
Kaptein
A
A
Laboratoires Glaxo-Wellcome, Centre de Recherche, ZA de Courtaboeuf, France.
Paillard
V
V
Saunders
M
M
D000595:Amino Acid Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009842:Oligopeptides; D010455:Peptides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014443:Tyrosine; C085706:FLAG peptide