STAT1 from the cell membrane to the DNA

The binding of interferons (IFNs) to their receptors leads to the phosphory lation and activation of signal transducers and activators of transcription (STATs), and their translocation from the cytoplasm to the nucleus. The me chanisms by which the STATs move to the nuclear pore are not, however, know n. Here it is shown that IFN-alpha and -gamma signalling and STAT1 transloc ation are independent of the actin cytoskeleton or microtubules, Using fluo rescence loss in photobleaching (FLIP) and fluorescence recovery after phot obleaching (FRAP) experiments, the mobility of a fusion protein of STAT1 wi th green fluorescent protein (STAT1-GFP) was compared with that of GFP and protein kinase C-GFP. In IFN-gamma -treated and control cells, cytoplasmic STAT1-GFP shows high, energy-independent, mobility comparable to that of fr eely diffusible GFP, A random walk model for movement of STAT1 from the pla sma membrane to the nuclear pore is, therefore, indicated. Nuclear STAT1-GF P showed similar high mobility, with exclusion from nucleoli, consistent wi th high rates of association and dissociation of STAT1-DNA and/or STAT1-pro tein complexes in the nucleoplasm of the cell.