Regulation of IL-3 receptor expression: evidence for a post-transcriptional mechanism that dominantly suppresses the expression of beta subunits.
The IL-3 receptor (IL-3R) is composed of alpha and beta subunits. Two homologous beta subunits of IL-3R are present in the mouse: AIC2A is the IL-3 specific beta subunit, and AIC2B is the common beta subunit shared by IL-3, IL-5 and granulocyte macrophage colony stimulating (GM-CSF) factor receptors. Both beta subunits form functionally indistinguishable high-affinity IL-3Rs with the same IL-3R specific alpha subunit (IL-3R alpha or SUT-1). Cell surface expression of the alpha and beta subunits of IL-3R was found to be diminished in an IL-3 non-responsive variant (MC/9.IL-4) derived from an IL-3-dependent mast cell line, MC/9. This IL-3R-defective phenotype was dominant based on cell fusion experiments. Moreover, regulatory mechanisms of the alpha and beta subunits are distinct since cell hybrids between MC/9.IL-4 and a CTLL-2 transfectant (CTLL/AS) expressing AIC2A and IL-3R alpha showed a significantly reduced expression of the AIC2A mRNA, while the IL-3R alpha expression was unchanged. Since transcription of both AIC2A and IL-3R alpha cDNAs in the CTLL/AS was driven by an artificial promoter, SR alpha, and nuclear run-off assays showed similar transcriptional rates of the AIC2A gene in both CTLL/AS and the cell hybrids between MC/9.IL-4 and CTLL/AS, the dominant suppression of the beta subunits is post-transcriptional and sequence-specific. A target sequence of the negative regulator must be present within 2756 bases of AIC2A mRNA, which is transcribed from the transfected cDNA in CTLL/AS cells. Similar dominant suppression of the beta subunit expression was also found in a B cell line WEHI231. As the negative regulator suppresses expression of the beta subunits of IL-3, IL-5 and GM-CSF receptors, it has the potential to eliminate all three high-affinity receptors simultaneously.
Hara
T
T
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
Miyajima
A
A
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002460:Cell Line; D053648:Cytokine Receptor Common beta Subunit; D007377:Interleukin-3; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D021122:Protein Subunits; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis* / Q000737:chemistry; D014162:Transfection
D002352:Carrier Proteins; D053648:Cytokine Receptor Common beta Subunit; D007377:Interleukin-3; D021122:Protein Subunits; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3; C072185:Csf2rb2 protein, mouse; C072186:Csf2rb protein, mouse