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 of polypeptide ligands, including interferon alpha (IFN-alpha) and IFN-gamma. We report here that the inactive Stat91 in the cytoplasm of untreated cells is a monomer and that upon IFN-gamma-induced phosphorylation it forms a stable homodimer. Only the dimer is capable of binding to a specific DNA sequence directing transcription. Through dissociation and reassociation assays, we show that dimerization of Stat91 is mediated through SH2-phosphotyrosyl peptide interactions. Dimerization involving SH2 recognition of specific phosphotyrosyl peptides may well provide a prototype for interactions among family members of STAT proteins to form different transcription complexes.
Shuai
K
K
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021.
Horvath
C M
CM
Huang
L H
LH
Qureshi
S A
SA
Cowburn
D
D
Darnell
J E
JE
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D007372:Interferons / Q000494:pharmacology*; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D019000:Phosphotyrosine; D011485:Protein Binding; D050794:STAT1 Transcription Factor; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004268:DNA-Binding Proteins; D008024:Ligands; D046911:Macromolecular Substances; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D019000:Phosphotyrosine; D014443:Tyrosine; D007372:Interferons