Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction

J Immunol. 1999 Apr 15;162(8):4385-9.

Abstract

A mutation in the human (hu) IL-4R alpha, Q576R, has been linked with allergy in humans. Increased sensitivity of patients cells with this mutation to IL-4 suggest that a Q576R change enhances IL-4 signaling. To directly test this hypothesis, we analyzed the ability of huIL-4R alpha cDNA bearing the Q576R and Y575F mutations to signal tyrosine phosphorylation, DNA-binding activity, proliferation, protection from apoptosis, and CD23 induction in response to huIL-4 in murine cells. Responses generated by the Q576R and Y575F mutants were similar to those of the wild-type receptor, using various concentrations of huIL-4 and times of stimulation. These results indicate that neither the Q576R nor the Y575F mutations have a significant direct effect on IL-4 signal transduction, and that hypersensitive induction of CD23 in cells derived from human allergy patients may be due to different and/or additional alterations in the IL-4 signaling pathway.

Publication types

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

MeSH terms

  • Amino Acid Substitution / genetics
  • Amino Acid Substitution / immunology
  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Arginine / genetics
  • Cell Line
  • DNA-Binding Proteins / biosynthesis
  • Glutamine / genetics
  • Humans
  • Hypersensitivity / genetics*
  • Hypersensitivity / immunology
  • Insulin Receptor Substrate Proteins
  • Lymphocyte Activation / genetics
  • Mice
  • Mutagenesis, Site-Directed / immunology*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Receptor, Insulin / metabolism
  • Receptors, IgE / biosynthesis
  • Receptors, Interleukin-4 / genetics*
  • Receptors, Interleukin-4 / physiology
  • STAT6 Transcription Factor
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Trans-Activators / metabolism
  • Tyrosine / genetics
  • Tyrosine / metabolism

Substances

  • DNA-Binding Proteins
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Phosphoproteins
  • Receptors, IgE
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Stat6 protein, mouse
  • Trans-Activators
  • Glutamine
  • Tyrosine
  • Arginine
  • Receptor, Insulin