HOW CELLS RESPOND TO INTERFERONSGeorge R. Stark, Ian M. Kerr, Bryan Williams et al.|Annual Review of Biochemistry|1998 Interferons play key roles in mediating antiviral and antigrowth responses and in modulating immune response. The main signaling pathways are rapid and direct. They involve tyrosine phosphorylation and activation of signal transducers and activators of transcription factors by Janus tyrosine kinases at the cell membrane, followed by release of signal transducers and activators of transcription and their migration to the nucleus, where they induce the expression of the many gene products that determine the responses. Ancillary pathways are also activated by the interferons, but their effects on cell physiology are less clear. The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interferons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells.Ian M. Kerr, R.E. Brown|Proceedings of the National Academy of Sciences|1978 A low molecular weight inhibitor of cell-free protein synthesis effective at subnanomolar concentrations is formed on incubation of cytoplasmic extracts from interferon-treated cells with double-stranded RNA and ATP. It can be conveniently synthesized by incubating a poly(I).poly(C)-Sepharose-bound enzyme fraction from such cells with [3H]- or [alpha- or gamma-32P]ATP. The radioactive inhibitor has been characterized by its behavior on DEAE-Sephadex in the presence of urea and on the basis of the products obtained on enzymic, alkaline, and sequential degradation by periodate oxidation and beta elimination. Its structure appears to be pppA2'p5'A2'p5'A. We have found no evidence for any modification or abnormality other than the 2'-5' linkage. On occasion the inhibitor preparations have included what seems to be the corresponding dimer (pppA2'p5'A), tetramer [ppp(A2'p)3A], pentamer [ppp(A2'p)4A], and higher oligomers in decreasing amounts. The trimer, tetramer, and pentamer are similar in activity, but the dimer is less potent if active at all.