Requirement of serine phosphorylation for formation of STAT-promoter complexes.
Members of the interleukin-6 family of cytokines bind to and activate receptors that contain a common subunit, gp130. This leads to the activation of Stat3 and Stat1, two cytoplasmic signal transducers and activators of transcription (STATs), by tyrosine phosphorylation. Serine phosphorylation of Stat3 was constitutive and was enhanced by signaling through gp130. In cells of lymphoid and neuronal origins, inhibition of serine phosphorylation prevented the formation of complexes of DNA with Stat3-Stat3 but not with Stat3-Stat1 or Stat1-Stat1 dimers. In vitro serine dephosphorylation of Stat3 also inhibited DNA binding of Stat3-Stat3. The requirement of serine phosphorylation for Stat3-Stat3.DNA complex formation was inversely correlated with the affinity of Stat3-Stat3 for the binding site. Thus, serine phosphorylation appears to enhance or to be required for the formation of stable Stat3-Stat3.DNA complexes.
Zhang
X
X
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Blenis
J
J
Li
H C
HC
Schindler
C
C
Chen-Kiang
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D007546:Isoquinolines; D009419:Nerve Tissue Proteins; D010879:Piperazines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA