Interferon-stimulated gene factor 3 (ISGF3), the primary transcription factor induced by interferon α, is a complex of four (113, 91, 84, and 48 kd) proteins. This paper reports that the 113, 91, and 84 kd (ISGF3α) proteins of ISGF3 contain conserved SH2 and SH3 domains. A specific interferon α-induced cytoplasmic protein tyrosine kinase(s) can form a transient complex with ISGF3α proteins. These ISGF3α proteins can be immunoprecipitated by anti-phosphotyrosine antibodies only after interferon α treatment. Phosphoamino acid analyses of 32P-labeled ISGF3α proteins confirm that ISGF3α proteins are directly tyrosine phosphorylated both in vitro and in vivo in response to interferon α, and this tyrosine phosphorylation can be inhibited by staurosporine and genistein. Phosphatase treatment of these ISGF3α proteins results in inhibition of ISGF3 complex formation in vitro. These observations indicate that interferon α-induced direct tyrosine phosphorylation of ISGF3α proteins is necessary for activation of the transcription factor ISGF3.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)