scholarly journals The basis for TCR-mediated regulation of the IL-2 receptor alpha chain gene: role of widely separated regulatory elements

2002 ◽  
Vol 21 (12) ◽  
pp. 3051-3059 ◽  
Author(s):  
H.-P. Kim
Keyword(s):  
Regulatory Elements ◽  
Chain Gene ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Receptor Alpha Chain

scholarly journals Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel.

1992 ◽  
Vol 12 (9) ◽  
pp. 4067-4075 ◽  
Author(s):  
T H Tan ◽  
G P Huang ◽  
A Sica ◽  
P Ghosh ◽  
H A Young ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Interleukin 2 ◽  
Regulatory Elements ◽  
Chain Gene ◽  
Nf Kappa B ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Alpha Gene ◽  
Receptor Alpha Chain

The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R alpha) gene contain a potent kappa B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa B-binding protein NF-kappa B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa B element in the IL-2R alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R alpha promoter, but not the kappa B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the kappa B site of the IL-2R alpha promoter. Finally, induction of surface IL-2R alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R alpha kappa B site. Our study identified c-Rel as one component of the Rel/NF-kappa B-family proteins involved in the kappa B-dependent activation of IL-2R alpha gene expression. Furthermore, our results suggest that a Re1NA-like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c-Re1 during T-cell activation.

Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel

1992 ◽  
Vol 12 (9) ◽  
pp. 4067-4075
Author(s):  
T H Tan ◽  
G P Huang ◽  
A Sica ◽  
P Ghosh ◽  
H A Young ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Interleukin 2 ◽  
Regulatory Elements ◽  
Chain Gene ◽  
Nf Kappa B ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Alpha Gene ◽  
Receptor Alpha Chain

The cis-acting control elements of the interleukin-2 receptor alpha-chain (IL-2R alpha) gene contain a potent kappa B-like enhancer whose activity can be induced by various mitogenic stimuli. Recent cloning of the p50 and p65 subunits of the kappa B-binding protein NF-kappa B complex revealed a striking sequence homology of these proteins with the c-rel proto-oncogene product (c-Rel). On the basis of this homology, we examined the potential role of c-Rel in controlling IL-2R alpha transcription. We now demonstrate that the recombinant human c-Rel protein binds to the kappa B element in the IL-2R alpha promoter and results in alteration of the DNA structure in the adjacent downstream regulatory elements containing the CArG box and the GC box. We found that human c-Rel can activate transcription from the IL-2R alpha promoter, but not the kappa B-containing human immunodeficiency virus type 1 promoter, upon cotransfection into Jurkat T cells. Furthermore, truncation of the carboxyl terminus of c-Rel results in a c-Rel mutant (RelNA) that (i) localizes exclusively in the nucleus and (ii) acts in synergy with wild-type c-Rel in activating transcription from the kappa B site of the IL-2R alpha promoter. Finally, induction of surface IL-2R alpha expression coincides with the induced levels of endogenous c-Rel and induced c-Rel binding to the IL-2R alpha kappa B site. Our study identified c-Rel as one component of the Rel/NF-kappa B-family proteins involved in the kappa B-dependent activation of IL-2R alpha gene expression. Furthermore, our results suggest that a Re1NA-like cellular factor (e.g., NF-kappa B p50 or p49 subunit) acts in synergy with c-Re1 during T-cell activation.

scholarly journals Delineation of an enhancerlike positive regulatory element in the interleukin-2 receptor alpha-chain gene.

1990 ◽  
Vol 10 (2) ◽  
pp. 850-853 ◽  
Author(s):  
B B Lin ◽  
S L Cross ◽  
N F Halden ◽  
D G Roman ◽  
M B Toledano ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Interleukin 2 ◽  
Chain Gene ◽  
Enhancer Activity ◽  
Enhancer Element ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Positive Regulatory Element ◽  
Receptor Alpha Chain

We have delineated a positive regulatory element in the interleukin-2 receptor alpha-chain gene (IL-2R alpha) between positions -299 and -243 that can potently activate a heterologous (herpesvirus thymidine kinase [tk]) promoter in phorbol myristate acetate (PMA)-induced Jurkat T cells and is functional when cloned in either orientation. This enhancerlike element contains a site (-268/-257) that can bind NF-kappa B; however, unlike the immunoglobulin kappa gene kappa B enhancer element, the IL-2R alpha kappa B-like site alone can only weakly activate a heterologous promoter. Adjacent 5' and 3' sequences also weakly activate the tk-CAT vector, but constructs combining the IL-2R alpha kappa B-like site plus adjacent 5' and 3' sequences potently activate gene expression. This combination of regions is essential for potent PMA-induced transcription from the tk promoter. Experiments using constructs in which IL-2R alpha upstream sequences are sequentially deleted suggested that there is a region 5' of position -299 which can suppress IL-2R alpha promoter and/or enhancer activity. Thus, it is possible that both positive and negative elements may be important in the regulation of IL-2R alpha gene transcription.

Discordance of the T-cell receptor alpha-chain gene in familial multiple sclerosis

Neurology ◽  
1992 ◽  
Vol 42 (4) ◽  
pp. 839-839 ◽  
Author(s):  
S. G. Lynch ◽  
J. W. Rose ◽  
J. H. Petajan ◽  
M. Leppert
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

Delineation of an enhancerlike positive regulatory element in the interleukin-2 receptor alpha-chain gene

1990 ◽  
Vol 10 (2) ◽  
pp. 850-853
Author(s):  
B B Lin ◽  
S L Cross ◽  
N F Halden ◽  
D G Roman ◽  
M B Toledano ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Interleukin 2 ◽  
Chain Gene ◽  
Enhancer Activity ◽  
Enhancer Element ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Interleukin 2 Receptor ◽  
Positive Regulatory Element ◽  
Receptor Alpha Chain

We have delineated a positive regulatory element in the interleukin-2 receptor alpha-chain gene (IL-2R alpha) between positions -299 and -243 that can potently activate a heterologous (herpesvirus thymidine kinase [tk]) promoter in phorbol myristate acetate (PMA)-induced Jurkat T cells and is functional when cloned in either orientation. This enhancerlike element contains a site (-268/-257) that can bind NF-kappa B; however, unlike the immunoglobulin kappa gene kappa B enhancer element, the IL-2R alpha kappa B-like site alone can only weakly activate a heterologous promoter. Adjacent 5' and 3' sequences also weakly activate the tk-CAT vector, but constructs combining the IL-2R alpha kappa B-like site plus adjacent 5' and 3' sequences potently activate gene expression. This combination of regions is essential for potent PMA-induced transcription from the tk promoter. Experiments using constructs in which IL-2R alpha upstream sequences are sequentially deleted suggested that there is a region 5' of position -299 which can suppress IL-2R alpha promoter and/or enhancer activity. Thus, it is possible that both positive and negative elements may be important in the regulation of IL-2R alpha gene transcription.

scholarly journals Cloning of rat interleukin 11 and interleukin 11 receptor alpha chain and analysis of their expression in rat uterus in the peri-implantation period

Reproduction ◽  
2001 ◽  
pp. 593-600 ◽  
Author(s):  
R Li ◽  
L Hartley ◽  
L Robb
Keyword(s):  
Rat Uterus ◽  
Rnase Protection ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Genes Encoding ◽  
Interleukin 11 ◽  
Implantation Period ◽  
Receptor Alpha Chain

Studies in mice have shown that interleukin 11 (IL-11) signalling is required for female fertility. In the absence of IL-11, decidualization is markedly retarded and implantation fails. IL-11 acts via a heterodimeric receptor composed of a ligand-specific receptor alpha chain (IL-11R alpha) and the signalling moiety gp130. This study reports the cloning of genes encoding rat IL-11 and IL-11R alpha. RNase protection was used to demonstrate that expression of IL-11 is upregulated in the rat uterus at the initiation of implantation at 5.5 days after mating. Expression of the genes encoding the two receptor components, IL11Ra and gp130, did not change throughout the peri-implantation period. In situ hybridization studies revealed that, as in mice, expression of IL-11 was high in the primary decidual zone at the time of the attachment reaction, whereas IL11Ra was expressed throughout primary and secondary decidua. Conservation of the temporal and spatial expression of IL-11 and IL-11R alpha in the uterus of the mouse and rat during the peri-implantation period will facilitate future studies investigating the role of IL-11 in fertility.

scholarly journals Ligand-induced assembly and activation of the gamma interferon receptor in intact cells.

1996 ◽  
Vol 16 (6) ◽  
pp. 3214-3221 ◽  
Author(s):  
E A Bach ◽  
J W Tanner ◽  
S Marsters ◽  
A Ashkenazi ◽  
M Aguet ◽  
...  
Keyword(s):  
Gamma Interferon ◽  
Beta Chain ◽  
Ifn Gamma ◽  
Intracellular Domain ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Gamma Receptor ◽  
Receptor Beta ◽  
Receptor Alpha Chain

Functionally active gamma interferon (IFN-gamma) receptors consist of an alpha subunit required for ligand binding and signal transduction and a beta subunit required primarily for signaling. Although the receptor alpha chain has been well characterized, little is known about the specific role of the receptor beta chain in IFN-gamma signaling. Expression of the wild-type human IFN-gamma receptor beta chain in murine L cells that stably express the human IFN-gamma receptor alpha chain (L.hgR) produced a murine cell line (L.hgR.myc beta) that responded to human IFN-gamma. Mutagenesis of the receptor beta-chain intracellular domain revealed that only two closely spaced, membrane-proximal sequences (P263PSIP267 and I270EEYL274) are required for function. Coprecipitation studies showed that these sequences are necessary for the specific and constitutive association of the receptor beta chain with the JAK-2 tyrosine kinase. These experiments also revealed that the IFN-gamma receptor alpha and beta chains are not preassociated on the surface of unstimulated cells but rather are induced to associate in an IFN-gamma-dependent fashion. A chimeric protein in which the intracellular domain of the beta chain was replaced by JAK-2 complemented human IFN-gamma signaling and biologic responsiveness in L.hgR. In contrast, a c-src-containing beta-chain chimera did not. These results indicate that the sole obligate role of the IFN-gamma receptor beta chain in signaling is to recruit JAK-2 into the ligand-assembled receptor complex.

Sign in / Sign up

Export Citation Format

Share Document