scholarly journals Ligand-stimulated tyrosine phosphorylation of the IL-2 receptor beta chain and receptor-associated proteins.

1991 ◽  
Vol 2 (1) ◽  
pp. 73-85 ◽  
Author(s):  
D A Shackelford ◽  
I S Trowbridge
Keyword(s):  
Signal Transduction ◽  
Tyrosine Phosphorylation ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Mouse Cell ◽  
Cellular Proteins ◽  
Tyrosine Kinase Domain ◽  
Beta Chain ◽  
High Affinity ◽  
Receptor Beta

Interleukin-2 (IL-2) stimulates the rapid phosphorylation on tyrosine of several specific cellular proteins. However, the high-affinity human IL-2 receptor, composed of an alpha (p55) and beta (p70/75) subunit, does not contain a cytoplasmic tyrosine kinase domain. In this study, we investigated the identities of the proteins phosphorylated on tyrosine in response to IL-2 stimulation to examine possible pathways of signal transduction. By the use of immunoblotting with anti-phosphotyrosine antibodies, we demonstrate that IL-2 augments tyrosine phosphorylation of the IL-2 receptor beta chain in human cell lines expressing either high-affinity (alpha/beta) receptors or only the beta chain. In IL-2-dependent mouse T cell lines, a 100,000-Da protein was phosphorylated on tyrosine in response to IL-2 and is proposed to be the mouse IL-2 receptor beta chain. Two other cellular proteins, pp55 and pp105 in human or pp55 and pp115 in mouse cell lines, were phosphorylated on tyrosine in response to IL-2 and coimmunoprecipitated with the high-affinity IL-2 receptor after chemical crosslinking of IL-2-stimulated cells. Thus, the IL-2 receptor may associate with additional subunits or with cellular proteins involved in signal transduction.

scholarly journals Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor.

1987 ◽  
Vol 165 (4) ◽  
pp. 1201-1206 ◽  
Author(s):  
R J Robb ◽  
W C Greene
Keyword(s):  
Cell Lines ◽  
Interleukin 2 ◽  
Essential Element ◽  
Receptor Complex ◽  
Beta Chain ◽  
Alpha Chain ◽  
Intracellular Degradation ◽  
High Affinity ◽  
Alpha Beta ◽  
Kinetics Of

High-affinity IL-2-R correspond to a membrane receptor complex composed of two different IL-2-binding proteins, the Tac antigen (alpha chain) and a 70-75 kD beta chain. Using cell lines that express either the alpha or the beta protein, we demonstrate that IL-2 internalization occurs when ligand is bound to the isolated beta chain, but not when it is bound to the isolated alpha chain. The kinetics of IL-2 internalization mediated by the intermediate-affinity beta chain were nearly identical to those of the high-affinity alpha/beta heterodimer (t1/2 of 10-15 min), and each type of receptor targeted the bound IL-2 for intracellular degradation in lysosomes. The beta chain thus appeared to provide the essential element necessary for ligand internalization by both types of IL-2-R.

scholarly journals Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling.

1992 ◽  
Vol 176 (5) ◽  
pp. 1265-1272 ◽  
Author(s):  
N Arima ◽  
M Kamio ◽  
K Imada ◽  
T Hori ◽  
T Hattori ◽  
...  
Keyword(s):  
Cell Lines ◽  
Interleukin 2 ◽  
Beta Chain ◽  
Alpha Chain ◽  
Functional Studies ◽  
High Affinity ◽  
The Third ◽  
Alpha Beta ◽  
D Cells ◽  
In Cells

Functional studies of the interleukin 2 receptor (IL-2R) of two (ED515-D and Kit225) IL-2-dependent and three (ED515-I, 3T3-alpha beta 11, and Hut102) IL-2-independent cell lines were done. All of these cell lines appeared to express high as well as low affinity IL-2R. However, ED515-I and 3T3-alpha beta 11, which expressed the IL-2R beta chain, did not bind IL-2 at all when IL-2 binding to their IL-2R alpha chain was blocked with anti-Tac monoclonal antibody, whereas the intermediate affinity binding in ED515-D, Kit225, and Hut102 cells remained. We tentatively called the high affinity IL-2R of the former cells pseudo-high affinity IL-2R. The dissociation constant of pseudo-high affinity IL-2R was higher than that of ordinary high affinity IL-2R. Internalization of cell-bound 125I-IL-2 into ED515-I and 3T3-alpha beta 11 cells was less efficient than that into ED515-D cells. The addition of IL-2 neither promoted cell growth nor upregulated IL-2R alpha chain expression in ED515-I and 3T3-alpha beta 11 cells. Furthermore, tyrosine phosphorylation of the cellular proteins (p120, p98, p96, p54, and p38) was induced or enhanced in response to the addition of IL-2 in ED515-D and Kit225 cells, but not in the cell lines expressing pseudo-high affinity IL-2R. Finally, 125I-IL-2 crosslinking followed by SDS-PAGE analysis showed an 80-kD band corresponding to p65 + IL-2, in addition to bands corresponding to IL-2R alpha and beta chain + IL-2 in cells bearing ordinary high affinity IL-2R but not in cells with pseudo-high affinity IL-2R. Taken together, we consider that another protein whose molecular mass is approximately 65 kD is functionally important in IL-2 binding and subsequent signal transduction and may be the third component of IL-2R.

scholarly journals High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells.

1986 ◽  
Vol 163 (3) ◽  
pp. 550-562 ◽  
Author(s):  
M Fujii ◽  
K Sugamura ◽  
K Sano ◽  
M Nakai ◽  
K Sugita ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Culture Fluid ◽  
Type I ◽  
Temperature Dependent ◽  
High Affinity ◽  
Human T Cell ◽  
Human T Cells ◽  
High Affinity Receptor

Receptor-mediated internalization and degradation of IL-2 were investigated in cell lines carrying human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I) and PHA-treated normal PBL. The HTLV-I-carrying cell lines ILT-Yan and TL-Mor, and the PBL expressed both high- and low-affinity IL-2-R. However, another HTLV-I-carrying T cell line, MT-1, expressed mainly low-affinity receptors. Greater than 50% of the IL-2 bound to high-affinity receptors was internalized within 10 min when these cells were incubated at 37 degrees C. The internalized IL-2 was rapidly degraded and the products were excreted into the culture fluid. The t1/2 of IL-2 degradation in these cells was estimated as 60-80 min at 37 degrees C. The internalization and degradation of IL-2 were both temperature dependent. Light-microscopic autoradiography with 3H-labeled IL-2 confirmed the internalization of IL-2, and suggested that some IL-2 might be carried to the nucleus.

Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's

Science ◽  
1989 ◽  
Vol 244 (4904) ◽  
pp. 551-556 ◽  
Author(s):  
M Hatakeyama ◽  
M Tsudo ◽  
S Minamoto ◽  
T Kono ◽  
T Doi ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Chain Gene ◽  
Beta Chain ◽  
Interleukin 2 Receptor ◽  
Receptor Beta

Abstract 2326: LTX-315, an oncolytic peptide, increases anticancer immunity mediated by CTLA4 blockade in an interleukin-2 receptor beta-chain-dependent manner

2016 ◽  
Author(s):  
Takahiro Yamazaki ◽  
Marie Vetizou ◽  
Camila Flores ◽  
Aurelien Marabelle ◽  
Baldur Sveinbjørnsson ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Dependent Manner ◽  
Beta Chain ◽  
Interleukin 2 Receptor ◽  
Ctla4 Blockade ◽  
Receptor Beta ◽  
Anticancer Immunity

scholarly journals gamma-c gene transfer into SCID X1 patients' B-cell lines restores normal high-affinity interleukin-2 receptor expression and function

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3108-3116 ◽  
Author(s):  
H Hacein-Bey ◽  
M Cavazzana-Calvo ◽  
F Le Deist ◽  
A Dautry-Varsat ◽  
C Hivroz ◽  
...  
Keyword(s):  
B Cells ◽  
Gene Transfer ◽  
B Cell ◽  
Cell Lines ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Chain Gene ◽  
High Affinity ◽  
And Function

SCID X1 is characterized by faulty T-cell and natural killer cell differentiation caused by mutation of the gamma-c chain gene encoding a number of multiple cytokine receptors (interleukin-2 [IL-2], IL-4, IL- 7, IL-9, and IL-15 receptors). To assess the feasibility of inducing long-term expression and function of the gamma-c chain, Epstein-Barr virus (EBV)-transformed B-cell lines from two patients with SCID X1 were transduced with a Moloney-derived retroviral vector containing the gamma-c chain cDNA. The viral LTR was used as the promoter. Immediately after two cycles of coculture with the psi-crip clone producing the MFG(B2)-gamma-c cDNA vector, gamma-c expression, assessed by detection of the mRNA and membrane protein expression, was found in 15% to 20% of cells. The degree of membrane expression was similar to that in control EBV-B cells. Expression increased steadily over 6 months, becoming detectable in 100% of cells, and remained stable thereafter for a total of 9 months, reflecting positive selection of transduced cells. A study of provirus integration sites showed multiple integration. The expressed gamma-c was functional, because it restored high-affinity IL- 2 receptor binding, IL-2 endocytosis, and IL-2-triggered phosphorylation of JAK-3 tyrosine kinase. Similar results were obtained with the two B-cell lines. These results show that efficient gamma-c gene transfer into B-cells lacking functional gamma-c is feasible and results in strong and stable expression of a functional gamma-c chain, apparently conferring a selective growth advantage in culture. Further in vitro studies of gamma-c gene transfer into gamma-c- hematopoietic progenitors are being conducted to assess the feasibility of correcting lymphocyte differentiation defects.

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