Abstract
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 α (IFN-α) and IFN-γ. We report here that the inactive Stat91 in the cytoplasm of untreated cells is a monomer and that upon IFN-γ-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 821-828 |
| Number of pages | 8 |
| Journal | Cell |
| Volume | 76 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 11 1994 |
Funding
We thank Drs. Ian Kerr and George Stark for providing U3A cells. We are grateful to Professor Brian Chait and the NIH-DRR Mass Spec resource for Mass Spectra. We thank Dr. Hidesaburo Hanafusa for providing GST-Src-SH2 fusion protein and Agustin France for excellent technical assistance. This work was supported by National Institutes of Health grants Al32489 (to J. E. D.) and GM47021 (to D. C.). C. M. H. is supported by a National Institutes of Health postdoctoral training award. K. S. and S. A. Q. are Cancer Research Institute Fellows.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology