J Asthma Allergy Clin Immunol.  2003 Jun;23(2):372-384.

Essential roles for ID-1 motif of interleukin-4 receptor alpha chain in interleukin-4 signaling

• Youn J
• Lee KH
• Hwang WY
• Paik DJ
• Chung HS

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.

Keyword

Interleukin-4; Interleukin-4 receptor; ID-1; STAT-6

MeSH Terms

Amino Acids, Acidic
Asthma
Clone Cells
DNA, Complementary
Electrophoretic Mobility Shift Assay
Gene Expression
Inflammation
Interleukin-2
Interleukin-4 Receptor alpha Subunit*
Interleukin-4*
Interleukins
Janus Kinases
Lymphoma
Mutagenesis, Site-Directed
Receptors, Interleukin-4
RNA
Sensitivity and Specificity
Serine
Amino Acids, Acidic
DNA, Complementary
Interleukin-2
Interleukin-4
Interleukin-4 Receptor alpha Subunit
Interleukins
Janus Kinases
RNA
Receptors, Interleukin-4
Serine