| 1957 |
Isaacs and Lindenmann describe interferon |
| 1975–1977 |
Oligonucleotide [2′-5′ oligoadenylates(s)] inhibitors of protein synthesis induced by IFN found |
| 1979 |
Actinomycin-sensitive IFN-β-dependent new protein induction shown |
| 1984 |
IFN-α-induced transcriptional stimulation of specific genes (ISGs) demonstrated; no new protein synthesis required |
| 1986–1988 |
IFN-dependent promoters identified (ISREs, interferon-stimulated response elements) |
| 1988–1989 |
IFN-α-induced ISRE binding protein complexes (ISGF3; E complex) in cytoplasm in 1–2 min; in nucleus in 5 min |
| 1989 |
Genetic selection system for defective IFN-induced transcription described and first cell mutant selected |
|
IFN-γ-dependent promoters (GAS, gamma IFN-activated sequences, and GAF, gamma IFN-activated factor) identified |
| 1989–1991 |
JAKs 1 and 2 and TYK2 identified |
| 1990 |
ISGF-3 partially purified; identified subunits 113, 91, 84, 48 |
| 1991 |
Noncomplementing mutant cells unresponsive to both IFN-α and IFN-γ described |
| 1992 |
cDNA clones sequenced later called STAT1 (a and b) and STAT2; RNA for IRF9 completing make up of ISGF3, establishing STAT family of proteins |
|
First IFN response mutant identified as Tyk2 by molecular complementation |
|
Upon IFN activation by IFN-α STAT1 and STAT2 are tyrosine phosphorylated; STAT1 also tyrosine phosphorylated after IFN-γ treatment |
| 1993–1994 |
Major signaling events driven by IFN and IL-6 pinpointed by molecular complementation of mutant cells |
| 1994 |
JAK3 described and sequenced |
| 1994–1995 |
STAT3, 4, 5A, 5B, and 6 all described and sequenced |
| 1995–1998 |
Functional and structural domains of STATs described |
| 1996 |
Drosophila STAT (dSTAT92E) first described; later studied extensively genetically |
|
Mouse genetics identifies physiological functions for all STATs in various specific cells |
| 1997 |
Negative regulation of pathways initially characterized |
| 1998 |
First crystal structures of STATs |
| 2000 |
Initial information that human mutations in JAKs and STATs and persistent activation of STATs cause disease |
|
First posttranslational modifications of STATs in addition to phosphorylations noted (methylation, acetylation, etc.) |
| 2001 |
Comprehensive gene target sets identified |
