Requirement of Serine Phosphorylation for Formation of STAT-Promoter Complexes

• Published in: Science (American Association for the Advancement of Science) Vol. 267; no. 5206; pp. 1990 - 1994
• Main Authors: Zhang, Xiaokui, Blenis, John, Li, Heng-Chun, Schindler, Chris, Chen-Kiang, Selina
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 31.03.1995; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Amino Acid Sequence; Animals; Antibodies; Base Sequence; Biological and medical sciences; Cell Line; Cell nucleus; Cell Nucleus - metabolism; Cell physiology; Cells; Cellular signal transduction; Ciliary Neurotrophic Factor; Cytochemistry; Cytokines; Cytoplasm - metabolism; DNA - metabolism; DNA-Binding Proteins - metabolism; Fear of Success; Fundamental and applied biological sciences. Psychology; Gels; Hep G2 cells; Humans; Interleukin-6; Interleukin-6 - metabolism; Interleukin-6 - pharmacology; Isoquinolines - pharmacology; Kinetics; Mice; Molecular and cellular biology; Molecular biology; Molecular Sequence Data; Nerve Tissue Proteins - pharmacology; Neurons; Phosphoamino acids; Phosphorylation; Piperazines - pharmacology; Promoter Regions, Genetic; Receptors; Responses to growth factors, tumor promotors, other factors; Serine - metabolism; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; Threonine - metabolism; Trans-Activators - metabolism; Tumor Cells, Cultured; Tyrosine - metabolism; Human; Interleukin 6; Signal transduction; Phosphorylation; Cell line; DNA; Cytokine; Molecular interaction; Molecular complex; Transcription factor; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7701321

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.