STAT1 from the cell membrane to the DNA.
The binding of interferons (IFNs) to their receptors leads to the phosphorylation and activation of signal transducers and activators of transcription (STATs), and their translocation from the cytoplasm to the nucleus. The mechanisms by which the STATs move to the nuclear pore are not, however, known. Here it is shown that IFN-alpha and -gamma signalling and STAT1 translocation are independent of the actin cytoskeleton or microtubules. Using fluorescence loss in photobleaching (FLIP) and fluorescence recovery after photobleaching (FRAP) experiments, the mobility of a fusion protein of STAT1 with 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 freely diffusible GFP. A random walk model for movement of STAT1 from the plasma membrane to the nuclear pore is, therefore, indicated. Nuclear STAT1-GFP showed similar high mobility, with exclusion from nucleoli, consistent with high rates of association and dissociation of STAT1-DNA and/or STAT1-protein complexes in the nucleoplasm of the cell.
Lillemeier
B F
BF
Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Köster
M
M
Kerr
I M
IM
D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005453:Fluorescence; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D004247:DNA; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D007371:Interferon-gamma; D008565:Membrane Proteins; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human