Figure 3.

Model of STAT1 import and export after IFNγ stimulation. The binding of IFN to the cell surface receptor causes the recruitment and phosphorylation of STAT1. Through spontaneous dissociation and reassociation, the activated STAT1 molecules constantly oscillate between the parallel and antiparallel dimer conformations. The importin-α recognizes and binds to the NLS on the STAT1 dimer. After binding to the STAT1 dimer, importin-α binds to importin-β in the cytoplasm. This complex (STAT1/importin-α/importin-β) interacts with the nuclear pore, and the movement that drives the import substrate complex into the nucleus appears to be generated between importin-β and structures of the nuclear pore. After interaction with the DNA and activation of transcription, STAT1 conformation shifts from parallel to antiparallel dimers, which is a conformation susceptible to dephosphorylation by the nuclear phosphatase TC45. Unphosphorylated STAT1 is then exported to the cytoplasm by exportin1.