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. 1995 Aug 1;92(16):7307–7311. doi: 10.1073/pnas.92.16.7307

Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.

C M Bacon 1, E F Petricoin 3rd 1, J R Ortaldo 1, R C Rees 1, A C Larner 1, J A Johnston 1, J J O'Shea 1
PMCID: PMC41328  PMID: 7638186

Abstract

Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily. We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and Tyk2, implicating these kinases in the immediate biochemical response to IL-12. Recently, transcription factors known as STATs (signal transducers and activators of transcription) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases. In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member, STAT4, and show that STAT4 expression is regulated by T-cell activation. Furthermore, we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4. These data, and the recent demonstration of JAK phosphorylation by IL-12, identify a rapid signal-transduction pathway likely to mediate IL-12-induced gene expression.

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Selected References

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