Association of the interleukin-4 receptor alpha chain with p47phox, an activator of the phagocyte NADPH oxidase in B cells.
Interleukin (IL)-4 plays an important role in IgE synthesis in B cells and in Th2 differentiation in T cells. IL-4 conducts its biological activities through binding to the IL-4 receptor (IL-4R) on the surface of target cells. IL-4R are thought to be composed of the IL-4R alpha chain (IL-4R alpha) and either the IL-2R gamma chain or the IL-13R alpha chain. We have previously shown that the membrane-proximal portion in the cytoplasmic domain of the human IL-4R alpha (hIL-4R alpha) is critical for proliferation, generation of germline epsilon transcript, and activation of STAT6, based on analyses of truncated hIL-4R alphas. In this study, we found that p47phox, an activator of the phagocyte NADPH oxidase, binds to this portion by the two-hybrid system. Furthermore, we observed the association of p47phox with the hIL-4R alpha in B cells derived from a normal donor. These results suggest that p47phox is involved in the signal transduction of IL-4 in B cells. However, activation of STAT6, CD23 expression, and IgE synthesis induced by IL-4 were not affected in p47phox-deficient patients, which raises the possibility that p47phox may be important in other signaling activities as well in B cells.
Izuhara
K
K
Department of Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. kizuhara@cclm.med.kyushu-u.ac.jp
Arinobu
Y
Y
Sumimoto
H
H
Nunoi
H
H
Takeya
R
R
Higuchi
K
K
Takeshige
K
K
Hamasaki
N
N
Harada
N
N
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D019255:NADPH Oxidases / Q000276:immunology / Q000378:metabolism*; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000276:immunology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology
D010750:Phosphoproteins; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1