Receptors for interleukin-3 (IL-3) and growth hormone mediate an IL-6-type transcriptional induction in the presence of JAK2 or STAT3

Blood. 1995 Sep 1;86(5):1671-9.

Abstract

To determine the specificity of signal transducer and activator of transcription (STAT) protein activation by box 3 motif-deficient hematopoietin receptors, expression vectors encoding the receptors for growth hormone, interleukin-3 (IL-3), and IL-4 were transiently transfected into COS-1 cells, together with expression vectors for Janus kinases (JAKs) and STAT proteins. Each receptor mediated a dose-dependent activation of STAT1 and STAT3, and for IL-3R and GHR this process was enhanced by JAK2. The data suggest that a box 3 motif in the cytoplasmic domain of the signal-transducing receptor to the JAK/STAT pathway. Transfection of the receptors, in combination with STAT3, into HepG2 cells reconstituted a cytokine-dependent stimulation of gene transcription through IL-6 response elements, providing evidence for a functional role of STAT3 in controlling gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular
  • Cell Line
  • Chlorocebus aethiops
  • Cytokines / pharmacology
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Gene Expression / drug effects
  • Humans
  • Interleukin-6 / pharmacology*
  • Janus Kinase 2
  • Kinetics
  • Liver Neoplasms
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins*
  • Receptors, Colony-Stimulating Factor / physiology
  • Receptors, Interleukin / drug effects
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-3 / biosynthesis
  • Receptors, Interleukin-3 / drug effects
  • Receptors, Interleukin-3 / physiology*
  • Receptors, Interleukin-4
  • Receptors, Somatotropin / biosynthesis
  • Receptors, Somatotropin / drug effects
  • Receptors, Somatotropin / physiology*
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Transcription, Genetic / drug effects*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Interleukin-6
  • Proto-Oncogene Proteins
  • Receptors, Colony-Stimulating Factor
  • Receptors, Interleukin
  • Receptors, Interleukin-3
  • Receptors, Interleukin-4
  • Receptors, Somatotropin
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2