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Published on: December 17, 2015
Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15
J A Johnston1, C M Bacon, D S Finbloom
1Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
The cytokines interleukin 2 (IL-2) and IL-15 have similar biological effects on T cells and bind common hematopoietin receptor subunits. Pathways that involve Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to be important for hematopoietin receptor signaling. In this study we identify the STAT proteins activated by IL-2 and IL-15 in human T cells. IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5, and DNA-binding complexes containing STAT3 and STAT5 were rapidly activated by these cytokines in T cells. IL-4 induced tyrosine phosphorylation and activation of STAT3 but not STAT5. JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. Hence, the JAK and STAT molecules that are activated in response to IL-2 and IL-15 are similar but differ from those induced by IL-4. These observations identify the STAT proteins activated by IL-2 and IL-15 and therefore define signaling pathways by which these T-cell growth factors may regulate gene transcription.
Insights
Interleukin 2 (IL-2) and IL-15 activate STAT3 and STAT5 in T cells, distinct from IL-4 signaling. This identifies key Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways for T-cell growth factors.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Interleukin 2 (IL-2) and IL-15 share biological effects on T cells, binding common receptor subunits.
- Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways are crucial for hematopoietin receptor signaling.
Purpose of the Study:
- To identify the specific STAT proteins activated by IL-2 and IL-15 in human T cells.
- To elucidate the distinct JAK-STAT signaling pathways employed by IL-2 and IL-15 compared to IL-4.
Main Methods:
- Analysis of tyrosine phosphorylation of STAT proteins in human T cells stimulated with IL-2, IL-15, and IL-4.
- Assessment of DNA-binding activity of activated STAT complexes.
- Investigation of JAK1 and JAK3 tyrosine phosphorylation in response to cytokine stimulation.
Main Results:
- IL-2 and IL-15 rapidly induced tyrosine phosphorylation and DNA-binding activation of STAT3 and STAT5 in T cells.
- IL-4 induced tyrosine phosphorylation and activation of STAT3, but not STAT5.
- Both IL-2 and IL-15 triggered tyrosine phosphorylation of JAK1 and JAK3.
Conclusions:
- The JAK and STAT molecules activated by IL-2 and IL-15 are similar but differ from those activated by IL-4.
- This study defines the specific STAT proteins and signaling pathways utilized by IL-2 and IL-15 for T-cell gene regulation.
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