Murine interleukin‐2 receptor subunits differentially detected with anti‐interleukin‐2 monoclonal antibodies

Takemoto, Hiroshi

doi:10.1016/0014-5793(89)80749-5

Cited by 3 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-2 mediates its biologic effects via the IL-2 receptor (IL-2R) complex. IL-2R is comprised of three distinct subunits: alpha, beta, and gamma chains (6,7). IL-2Rbeta and gamma are involved in several cytokinesignaling pathways including IL-4, IL-7, IL-9, IL-15 and IL-21 (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

The role of interleukin-2 receptor alpha in cancer

Kuhn

Dou²

2005

Front Biosci

View full text Add to dashboard Cite

Interleukin-2 (IL-2) is the major growth factor for activated T-lymphocytes and stimulates clonal expansion and maturation of these lymphocytes. IL-2 binds to its receptor complex, IL-2Ralpha, beta, and gamma chains, and exerts its effect via second messengers, mainly tyrosine kinases, which ultimately stimulate gene expression. The heterotrimerization of the receptor chains leads to high affinity binding for IL-2. The functional importance of IL-2Ralpha in hematopoietic cell systems is well known. However, the potential role that IL-2Ralpha plays in tumorigenesis is still not fully elucidated. Il-2Ralpha expression has been found in many types of cancers, including leukemia, lymphoma, lung, breast, head-and-neck and prostate. Recent evidence shows that high expression of IL-2Ralpha in tumors correlates with a poor prognosis for the patient. This review details the current known functions of IL-2Ralpha in cancer cells and some of the therapies used to combat IL-2Ralpha-mediated cell signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

The role of interleukin-2 receptor alpha in cancer

Kuhn

Dou²

2005

Front Biosci

View full text Add to dashboard Cite

show abstract

“…IL-2 medicates its biologic effects by binding to the IL-2 receptor (IL-2R) complex. IL-2R is composed of three chains: a, b, and g [Sharon et al, 1986;Takemoto, 1989]. The a chain (CD25þ, Tac, p55) is involved in IL-2 and IL-15 signaling, while IL-2Rb and g chains are involved in several cytokine-signaling pathways including IL-4, IL-7, IL-9, IL-15, and IL-21 Russell et al, 1993;Anderson et al, 1995;Kimura et al, 1995].…”

mentioning

confidence: 99%

Direct inhibition of interleukin‐2 receptor α‐mediated signaling pathway induces G₁ arrest and apoptosis in human head‐and‐neck cancer cells

Kuhn

Dou

2005

J of Cellular Biochemistry

View full text Add to dashboard Cite

Overexpression of the interleukin-2 receptor (IL-2R) alpha chain in tumor cells is associated with tumor progression and a poor patient prognosis. IL-2Ralpha is responsible for the high affinity binding of the receptor to IL-2, leading to activation of several proliferative and anti-apoptotic intracellular signaling pathways. We have previously shown that human squamous cell carcinoma of a head-and-neck line (PCI-13) genetically engineered to overexpress IL-2Ralpha exhibit increased transforming activity, proliferation, and drug resistance, compared to the vector control cells (J Cell Biochem 2003;89:824-836). In this study, we report that IL-2Ralpha(+) cells express high levels of total and phosphorylated Jak3 protein and are more resistant to apoptosis induced by a Jak3 inhibitor than the control LacZ cells. Furthermore, we used daclizumab, a monoclonal antibody specific to IL-2Ralpha, and determined the effects of IL-2Ralpha inhibition on cell cycle and apoptosis as well as the involvement of potential cell cycle and apoptosis regulatory proteins. We found that daclizumab induces G(1) arrest, associated with down-regulation of cyclin A protein, preferentially in IL-2Ralpha(+) cells, but not in LacZ cells. In addition, daclizumab activates apoptotic death program via Bcl-2 down-regulation preferentially in IL-2Ralpha(+) cells. Finally, daclizumab also sensitizes IL-2Ralpha(+) cells to other apoptotic stimuli, although the effect is moderate. These results indicate that daclizumab inhibits the proliferative potential of IL-2Ralpha(+) cells via inhibition of cell cycle progression and induction of apoptosis.

show abstract

Two Distinct P70 Interleukin-2 Receptors on a Murine Large Granular Lymphocyte Clone Y479

Takemoto¹,

Yagi²,

Harada³

et al. 1991

Immunological Investigations

Self Cite

View full text Add to dashboard Cite

A continuous cloned cell line (Y479) was established by culturing normal mouse spleen cells in a high concentration of interleukin-2 (IL-2). Y479 cells showed morphological characteristics of large granular lymphocyte with the phenotypes of Thy-1.2+, T3+, Lyt-1-, Lyt-2-, L3T4-, B220-, AsGM1+, LFA-1+, and TcRV beta 8-. The Y479 cells required a high concentration of IL-2 for their growth but did not express detectable p55 IL-2 receptor (IL-2R) although they bound IL-2 with high and low affinities. Analysis of the IL-2 binding proteins on the Y479 cells revealed that both the high and low affinity receptors consisted only of 70 kDa protein. Analysis of the 70 kDa protein was performed using five monoclonal antibodies (L15, L20, L23, L34, and L61) against human recombinant IL-2. Although they recognized different epitopes, all monoclonal antibodies immunoprecipitated 70 kDa IL-2R that was cross-linked with radioiodinated IL-2. The supernatant after immunoprecipitation with L61 still contained IL-2/IL-2R complex that was L23-reactive, and the supernatant after immunoprecipitation with L23 contained L61-reactive IL-2/IL-2R complex, whereas L15 immunoprecipitated almost all the complex. Limited digestion of IL-2-cross-linked Y479 cells with trypsin caused the liberation of 45 kDa IL-2R fragment cross-linked with IL-2. This complex was immunoprecipitated by L15 or L61 but not by L23. These results suggest that there are at least two distinct 70 kDa IL-2R on the surface of Y479 cells.

show abstract

Murine interleukin‐2 receptor subunits differentially detected with anti‐interleukin‐2 monoclonal antibodies

Cited by 3 publications

References 16 publications

The role of interleukin-2 receptor alpha in cancer

The role of interleukin-2 receptor alpha in cancer

Direct inhibition of interleukin‐2 receptor α‐mediated signaling pathway induces G₁ arrest and apoptosis in human head‐and‐neck cancer cells

Two Distinct P70 Interleukin-2 Receptors on a Murine Large Granular Lymphocyte Clone Y479

Contact Info

Product

Resources

About

Murine interleukin‐2 receptor subunits differentially detected with anti‐interleukin‐2 monoclonal antibodies

Cited by 3 publications

References 16 publications

The role of interleukin-2 receptor alpha in cancer

The role of interleukin-2 receptor alpha in cancer

Direct inhibition of interleukin‐2 receptor α‐mediated signaling pathway induces G1 arrest and apoptosis in human head‐and‐neck cancer cells

Two Distinct P70 Interleukin-2 Receptors on a Murine Large Granular Lymphocyte Clone Y479

Contact Info

Product

Resources

About

Direct inhibition of interleukin‐2 receptor α‐mediated signaling pathway induces G₁ arrest and apoptosis in human head‐and‐neck cancer cells