STAT3 forms stable homodimers in the presence of divalent cations prior to activation.

We present evidence that the transcription factor STAT3, derived from uninduced cells, can form stable homodimers, which are independent of the tyrosine phosphorylation status of the protein. The strong interaction, which is resistant to many denaturing agents, is dependent on the presence of divalent cations. The presence of the homodimer was initially observed in immunoprecipitates of STAT3 and was detected upon fractionation of cell lysates. These dimers are different in structure from dimers observed after cytokine stimulation of cells, which results in tyrosine phosphorylation of STAT3 and dimerization involving the SH2 domain of STAT3.