Essential roles for ID-1 motif of interleukin-4 receptor alpha chain in interleukin-4 signaling / 천식및알레르기
Journal of Asthma, Allergy and Clinical Immunology
;
: 372-384, 2003.
Article
in Korean
| WPRIM
| ID: wpr-20914
ABSTRACT
BACKGROUND:
Interleukin (IL)-4 is a pleiotropic cytokine that plays an important role in the pathogenesis of the allergic inflammation and asthma. Upon IL-4 receptor (IL-4R) engagement, a variety of signaling mediators, such as JAK kinases and STAT-6 are activated, leading to induction of IL-4 target gene expression including CD23 and germline C epsilon transcription. The function of a membrane-proximal domain of IL-4Ra, termed ID-1, remains to be characterized to date.OBJECTIVE:
To assess whether the ID-1 domain mediates the induction of IL-4 target gene expression in a STAT-6-dependent manner.METHODS:
The intracellular region of IL-4Ralpha was translationally fused to the extracellular region of IL-2Rbeta to provide ligand specificity to IL-2. Acidic amino acids and serine residues in the ID-1 domain of the chimeric receptor were substituted by site-directed mutagenesis. These receptor cDNAs were stably transfected to M12.4.1 murine B lymphoma cells. Following IL-2 stimulation, wild type and mutant clones for the ID-1 motif were subjected to FACS. RNA blotting and elecroporetic mobility shift assays to address the levels of CD23, germline C epsilon and STAT-6 inductions, respectively.RESULTS:
ID-1 mutant clones were defective in gene induction of CD23 and germline C epsilon in response to IL-2 stimulation, as compared with wildtype clones. Moreover, IL-2-mediated STAT-6 activation was abolished in ID-1 mutant clones.CONCLUSION:
These results demonstrate that the ID-1 domain of IL-4Ra is essential to induce IL-4 target gene expression through a STAT-6-dependent pathway.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Asthma
/
Serine
/
RNA
/
Gene Expression
/
Mutagenesis, Site-Directed
/
Sensitivity and Specificity
/
Interleukins
/
Interleukin-4
/
Interleukin-2
/
Clone Cells
Type of study:
Diagnostic study
Language:
Korean
Journal:
Journal of Asthma, Allergy and Clinical Immunology
Year:
2003
Type:
Article
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