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Functional roles of STAT family proteins: lessons from knockout mice
1Department of Biochemistry, CREST of Japan Science and Technology Corporation, Hyogo College of Medicine, Nishinomiya.
Abstract:
STAT (signal transducers and activators of transcription) proteins are activated in response to a large number of cytokines, growth factors, and hormones. Upon activation following the binding of ligands to their receptors, STAT proteins dimerize, translocate to the nucleus, and bind to the promoters of specific target genes. To date, seven mammalian members of the STAT family have been identified. Although some cytokines and growth factors can activate multiple STAT proteins, some STATs are activated with considerable specificity. The physiological role of each individual STAT protein is now being examined through the study of "knockout" mice, harboring a null allele for the particular gene. STAT1-deficient mice exhibit a selective signaling defect in response to interferons. STAT4 and STAT6 are essential for Thl-and Th2-responses, respectively. STAT5a-deficient mice exhibit defective mammary gland development. A study of STAT5b-deficient mice indicates that STAT5b mediates the sexually dimorphic effects of growth hormone in the liver. STAT5a and 5b also play different biological roles in the immune system. STAT3-deficient mice die during early embryogenesis, but the role of STAT3 in adult tissues can be assessed by utilizing the CreloxP recombination system to ablate the gene later in life. Analyses of tissue-specific STAT3-deficient mice indicate that STAT3 plays a crucial role in a variety of biological functions, including cell growth, suppression of apoptosis, and cell motility.
Insights
Signal transducers and activators of transcription (STAT) proteins regulate gene expression. Knockout mouse studies reveal specific roles for STAT proteins in immunity, development, and cell growth.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Genetics
Background:
- Signal transducers and activators of transcription (STAT) proteins are key mediators of cellular responses to extracellular signals.
- Seven mammalian STAT proteins have been identified, each playing distinct roles in biological processes.
Purpose of the Study:
- To elucidate the specific physiological functions of individual STAT proteins.
- To investigate the roles of STAT proteins in various biological contexts using genetic models.
Main Methods:
- Utilizing knockout mouse models to study STAT protein function.
- Employing Cre-loxP recombination systems for tissue-specific gene ablation.
Main Results:
- STAT1 deficiency impairs interferon signaling.
- STAT4 and STAT6 are critical for Th1 and Th2 immune responses, respectively.
- STAT5a and STAT5b have distinct roles in mammary gland development, growth hormone signaling, and immune function.
- STAT3 is essential for embryonic development and plays vital roles in adult cell growth, apoptosis suppression, and motility.
Conclusions:
- Individual STAT proteins possess unique and essential functions in mammalian physiology.
- Genetic studies in mice are crucial for understanding the complex roles of STAT proteins in health and disease.