Editors' ChoiceCytokine Signals

Importin α Targets STAT Dimers to Nucleus

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Science's STKE  20 Aug 2002:
Vol. 2002, Issue 146, pp. tw306
DOI: 10.1126/stke.2002.146.tw306

STATs (signal transducers and activators of transcription) become activated when they are phosphorylated by tyrosine kinases that associate with activated cytokine receptors. The phosphorylated STATs form homodimers or heterodimers that translocate to the nucleus and regulate gene expression. Recent work identified nuclear localization signals (NLSs) in STATS 1 and 2 and now Fagerlund et al. confirm that these protein domains are critical for nuclear localization. They studied STAT1 homodimers or STAT1-STAT 2 heterodimers and their interaction with importin α, a key component of the nuclear transport machinery that binds NLSs on proteins that are moved into the nucleus through the nuclear pore complex. Only the phosphorylated, dimeric STATs interacted with a fusion protein of importin α linked to glutathione S-transferase or localized with importin α in transfected cells. Mutation of the NLS in the STATs prevented interaction with importin α. Many studies have shown that phosphorylation and dimerization of STATs are essential activation events. The altered affinity for binding to importin α acquired by the activated dimers provides a mechanism by which the activation signal is recognized in the nucleus.

R. Fagerlund, K. Melén, L. Kinnunen, I. Julkunen, Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin α5, J. Biol. Chem. 277, 30072-30078 (2002). [Abstract] [Full Text]

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