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Cytoplasmic STAT proteins associate prior to activation
S Haan1, M Kortylewski, I Behrmann
1Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Abstract:
The commonly accepted model of STAT factor activation at the cytoplasmic part of the receptor assumes that signal transducers and activators of transcription (STATs) are recruited from a cytoplasmic pool of monomeric STAT proteins. Based on a previous observation that non-phosphorylated STAT3-Src homology 2 domains dimerize in vitro, we investigated whether the observed dimerization is of physiological relevance within the cellular context. We show that STAT1 and STAT3 are pre-associated in non-stimulated cells. Apparently, these complexes are not able to translocate into the nucleus. We provide evidence that the event of STAT activation is more complex than previously assumed.
Insights
Signal transducers and activators of transcription (STATs) exist as pre-associated complexes in non-stimulated cells. These STAT1 and STAT3 complexes do not translocate to the nucleus, indicating a more complex activation process than previously understood.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Signal transduction
Background:
- The canonical model posits that signal transducers and activators of transcription (STATs) are recruited as monomers from the cytoplasm to activated receptors.
- Previous in vitro studies indicated that non-phosphorylated STAT3-Src homology 2 domains can dimerize.
Purpose of the Study:
- To investigate the physiological relevance of STAT dimerization within the cellular context.
- To determine if STAT proteins exist as pre-associated complexes in non-stimulated cells.
Main Methods:
- Cellular assays to examine STAT protein interactions.
- Investigating the localization and translocation of STAT complexes.
Main Results:
- Signal transducers and activators of transcription (STATs), specifically STAT1 and STAT3, are found to be pre-associated in non-stimulated cells.
- These pre-associated STAT complexes are unable to translocate into the nucleus in their non-phosphorylated state.
Conclusions:
- The current model of STAT activation requires revision.
- STAT activation is a more intricate process than the simple recruitment of monomeric units.
- Pre-association of STAT proteins suggests alternative regulatory mechanisms prior to receptor stimulation.