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

Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7307-11. doi: 10.1073/pnas.92.16.7307.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Interleukin-12 / pharmacology*
  • Janus Kinase 2
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism
  • Proto-Oncogene Proteins*
  • Receptors, IgG / genetics
  • STAT4 Transcription Factor
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • TYK2 Kinase
  • Trans-Activators / metabolism*
  • Tyrosine / metabolism*

Substances

  • DNA-Binding Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, IgG
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • Trans-Activators
  • Interleukin-12
  • Tyrosine
  • DNA
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2
  • TYK2 Kinase
  • TYK2 protein, human