The role of Stat5a and Stat5b in signaling by IL-2 family cytokines.
The activation of Stat5 proteins (Stat5a and Stat5b) is one of the earliest signaling events mediated by IL-2 family cytokines, allowing the rapid delivery of signals from the membrane to the nucleus. Among STAT family proteins, Stat5a and Stat5b are the two most closely related STAT proteins. Together with other transcription factors and co-factors, they regulate the expression of the target genes in a cytokine-specific fashion. In addition to their activation by cytokines, activities of Stat5a and Stat5b, as well as other STAT proteins, are negatively controlled by CIS/SOCS/SSI family proteins. The outcome of Stat5 activation in regulating expression of target genes varies, depending upon the complexity of the promoter region of target genes and the other signaling pathways that are activated by each cytokine as well. Here, we mainly focus on the IL2-/IL-2 receptor system, as it is one of the best-studied systems that depend on Stat5-mediated signals. We will summarize what we have learned about the molecular mechanisms of how Stat5 is activated by IL-2 family cytokines from in vitro biochemical studies as well as the role that is played by Stat5 in each of the cytokine signaling pathways from in vivo gene-targeting analyses. Oncogene (2000).
Lin
J X
JX
Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg. 10/Rm. 7N252, 9000 Rockville Pike, Bethesda, Maryland MD 20892-1674, USA.
Leonard
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance; D007157:Immunologic Surveillance; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D053616:Janus Kinase 3; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3