Functional importance of Stat3 tetramerization in activation of the alpha 2-macroglobulin gene.

A tetrameric Stat3 complex was found to be essential in transfection experiments for maximal interleukin-6-inducible activation of alpha2-macroglobulin gene promoter. Stable tetramer formation of purified phosphorylated Stat3 was dependent on protein.protein interaction involving the N-terminal domain of Stat3. The functional importance of tetramer formation was shown by the decreased levels of transcriptional activation associated with hypomorphic mutations in N-terminal residues.