Inhibition of cytokines and JAK-STAT activation by distinct signaling pathways Academic Article Article uri icon


MeSH Major

  • Gene Expression Regulation
  • Genetic Therapy
  • Inflammation
  • Tumor Necrosis Factor-alpha


  • An important component of cytokine regulation of cell growth and differentiation is rapid transcriptional activation of genes by the JAK-STAT (signal transducer and activator of transcription) signaling pathway. Ligation of cytokine receptors results in tyrosine phosphorylation and activation of receptor-associated Jak protein tyrosine kinases and cytoplasmic STAT transcription factors, which then translocate to the nucleus. We describe the interruption of cytokine triggered JAK-STAT signals by cAMP, the calcium ionophore ionomycin, and granulocyte/macrophage colony-stimulating factor. Jak1 kinase activity, interleukin 6-induced gene activation, Stat3 tyrosine phosphorylation, and DNA-binding were inhibited, as was activation of Jak1 and Stat1 by interferon gamma. The kinetics and requirement for new RNA and protein synthesis for inhibition of interleukin 6 by ionomycin and GM-CSF differed, but both agents increased the association of Jak1 with protein tyrosine phosphatase ID (SH2-containing phosphatase 2). Our results demonstrate that crosstalk with distinct signaling pathways can inhibit JAK-STAT signal transduction, and suggest approaches for modulating cytokine activity during immune responses and inflammatory processes.

publication date

  • September 3, 1996



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1073/pnas.93.18.9499

PubMed ID

  • 8790359

Additional Document Info

start page

  • 9499

end page

  • 504


  • 93


  • 18