INTERFERON ACTIVATION OF THE TRANSCRIPTION FACTOR STAT91 INVOLVES DIMERIZATION THROUGH SH2-PHOSPHOTYROSYL PEPTIDE INTERACTIONS

Stat91 (a 91 kd protein that acts as a signal transducer and activator of transcription) is inactive in the cytoplasm of untreated cells but is activated by phosphorylation on tyrosine in response to a number o f polypeptide ligands, including interferon alpha (IFN-alpha) and lFN- gamma. We report here that the inactive Stat91 in the cytoplasm of unt reated cells is a monomer and that upon IFN-gamma-induced phosphorylat ion it forms a stable homodimer. Only the dimer is capable of binding to a specific DNA sequence directing transcription. Through dissociati on and reassociation assays, we show that dimerization of Stat91 is me diated through SH2-phosphotyrosyl peptide interactions. Dimerization i nvolving SH2 recognition of specific phosphotyrosyl peptides may well provide a prototype for interactions among family members of STAT prot eins to form different transcription complexes.