Binding of IL-4 to the IL-13Ralpha(1)/IL-4Ralpha receptor complex leads to STAT3 phosphorylation but not to its nuclear translocation

FEBS Lett. 1999 Dec 24;464(1-2):91-6. doi: 10.1016/s0014-5793(99)01680-4.

Abstract

Interleukin-4 (IL-4) is a pleiotropic cytokine, which acts on both hematopoietic and non-hematopoietic cells, through different types of receptor complexes. In this study, we report that in human B cells, IL-4 caused rapid phosphorylation of Janus kinase (JAK) 1 and JAK3 tyrosine kinases. In keratinocytes, the hematopoietic-specific receptor common gamma(c) chain is not expressed and the IL-13 receptor alpha(1) (IL-13Ralpha(1)) participates in IL-4 signal transduction. In keratinocytes, IL-4 induced JAK1 and JAK2 phosphorylation but, unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling. In both cell types, IL-4 induced phosphorylation and DNA binding activation of the signal transducer and activator of transcription (STAT) 6 protein. Furthermore, IL-4 stimulation of keratinocytes also induced tyrosine phosphorylation of STAT3 which was found to bind to the phosphorylated IL-13Ralpha(1). STAT3 however did not significantly translocate to the nucleus, nor did it bind with high affinity to target DNA sequences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Nucleus / metabolism*
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Fluorescent Antibody Technique
  • Humans
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / metabolism*
  • Keratinocytes / metabolism
  • Lymphocytes / metabolism
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4 / metabolism*
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism*

Substances

  • DNA-Binding Proteins
  • IL13RA1 protein, human
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Interleukin-4
  • DNA
  • Protein-Tyrosine Kinases