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J Biol Chem, Vol. 273, Issue 36, 22962-22968, September 4, 1998

Activation of the Janus Kinase/Signal Transducer and Activator of Transcription Pathway by Osmotic Shock

Petros GatsiosDagger , Lara TerstegenDagger §, Freimut Schliess, Dieter Häussinger, Ian M. Kerrparallel , Peter C. HeinrichDagger , and Lutz GraeveDagger

From the Dagger  Institute of Biochemistry, Rheinisch-Westfälische Technische Hochschule Aachen, 52057 Aachen, Germany,  Medizinische Klinik der Heinrich-Heine-Universität, 40225 Düsseldorf, Germany, § Interdisziplinäres Zentrum für Klinische Forschung (BIOMAT), Rheinisch-Westfälische Technische Hochschule Aachen, 52057 Aachen, Germany, and the parallel  Imperial Cancer Research Fund, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom

Numerous cytokines, growth, and differentiation factors elicit their intracellular responses via Janus tyrosine kinases (Jaks) and transcription factors of the STAT (signal transducer and activator of transcription) family. Additionally, environmental stress (UV light, heat, aniso-osmolarity, and radicals) has recently been shown to activate intracellular signaling cascades such as the stress-activated protein kinases and nuclear factor-kappa B. In this study, we demonstrate that in different cell lines a particular stress, namely hyperosmolarity, results in tyrosine phosphorylation of the Janus kinases Jak1, Jak2, and Tyk2 and in the activation of STAT1 and/or STAT3. Both transcription factors are phosphorylated at a specific tyrosine residue and translocation to the nucleus was demonstrated by the use of a STAT3/green fluorescent protein fusion protein. A prominent role for Jak1 in the activation of STATs by hypertonicity was demonstrated by the use of Jak-deficient cell lines. Stress-activated STAT1 and STAT3 transactivate a reporter gene containing the acute-phase response element of the rat alpha 2-macroglobulin promoter. Experiments using a diffusible solute suggest that not the increase in intracellular osmolarity but the resultant cell shrinkage is the trigger for Jak/STAT activation.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.


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