Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction.
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.
Wang
H Y
HY
Department of Immunology, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20855, USA.
Shelburne
C P
CP
Zamorano
J
J
Kelly
A E
AE
Ryan
J J
JJ
Keegan
A D
AD
D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001120:Arginine / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005973:Glutamine / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D055504:Insulin Receptor Substrate Proteins; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D016297:Mutagenesis, Site-Directed / Q000276:immunology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis; D019948:Receptors, Interleukin-4 / Q000235:genetics* / Q000502:physiology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D005973:Glutamine; D014443:Tyrosine; D001120:Arginine; D011972:Receptor, Insulin