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 acti vation of Stat3 and Stat1, two cytoplasmic signal transducers and acti vators of transcription (STATs), by tyrosine phosphorylation. Serine p hosphorylation 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 vi tro serine dephosphorylation of Stat3 also inhibited DNA binding of St at3-Stat3. The requirement of serine phosphorylation for Stat3-Stat3.D NA complex formation was inversely correlated with the affinity of Sta t3-Stat3 for the binding site. Thus, serine phosphorylation appears to enhance or to be required for the formation of stable Stat3-Stat3 DNA complexes.