Experimental Regulation of STAT Gene Expression Reveals an Involvement of STAT5 in Interleukin-4-Driven Cell Proliferation
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Karlheinz Friedrich
Abstract
The precise roles of signal transducers and activators of transcription (STATs) in cytokinetriggered control of cell physiology are not sufficiently well understood. We have established cell lines in which the individual functional contributions of STAT6 and STAT5a/b to interleukin(IL) 3 and -4-dependent processes can be readily studied. Mutants of STAT6, STAT5a and 5b lacking the transcriptional transactivation domain were fused to the green fluorescent protein (GFP) and expressed in the murine proB cell line Ba/F3 in a regulatable fashion. The expression of these truncated STAT variants could be tightly controlled over a wide range by doxycycline in the medium. They specifically bound to cognate DNA elements upon cytokine stimulation and acted dominantnegatively on the transcription of respective reporter genes in response to IL-3 and -4. The system was applied to the question of STAT contributions to cytokinedependent cell proliferation. Expression of dominantnegative STAT6 had no significant effect on cell growth in response to both IL-3 and IL-4. In contrast, truncated STAT5 interfered with cell proliferation in response to IL-3, and, interestingly, also to IL-4. The results support our earlier findings on a role of STAT5 in IL-4-induced intracellular signaling and indicate that STAT5b in particular is involved in IL-4 receptortriggered control of cell proliferation.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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- Highlight: Glycobiology
- O-Glycosylation of the Mucin Type
- Glycoproteins from Insect Cells: Sialylated or Not?
- Congenital Disorders of Glycosylation: Glycosylation Defects in Man and Biological Models for Their Study
- Mitochondrial Single-Stranded DNA-Binding Proteins: in Search for New Functions
- Do Rodent and Human Brains Have Different N-Glycosylation Patterns?
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- Pathways of Mucin O-Glycosylation in Normal and Malignant Rat Colonic Epithelial Cells Reveal a Mechanism for Cancer-Associated Sialyl-Tn Antigen Expression
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- Structural Characterization of Fucose-Containing Oligosaccharides by High-Performance Liquid Chromatography and Matrix-Assisted Laser Desorption/ Ionization Time-of-Flight Mass Spectrometry
- Anencephaly: Structural Characterization of Gangliosides in Defined Brain Regions
- Acidic Glycerol Lipids of Trichomonas vaginalis and Tritrichomonas foetus
- Stimulation of Acid Sphingomyelinase Activity by Lysosomal Lipids and Sphingolipid Activator Proteins
- Biosynthesis of N-Acetylneuraminic Acid in Cells Lacking UDP-N-Acetylglucosamine 2-Epimerase/ N-Acetylmannosamine Kinase
- Synthesis of Nucleotide-Activated Oligosaccharides by ?-Galactosidase from Bacillus circulans
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- Experimental Regulation of STAT Gene Expression Reveals an Involvement of STAT5 in Interleukin-4-Driven Cell Proliferation
