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.

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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