Molecular Analysis of the Interleukin‐2 System

Taniguchi, Tadatsugu; Matsui, Hiroshi; Fujita, Takashi; Hatakeyama, Masanori; Kashima, Nobukazu; Fuse, Akira; Hamuro, Junji; Nishi-Takaoka, Chikako; Yamada, Gen

doi:10.1111/j.1600-065x.1986.tb01497.x

Cited by 85 publications

(28 citation statements)

References 43 publications

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“…Interleukin 2 (IL-2) plays a critical role in regulating the proliferation and differentiation of hematopoietic cells (33,38). IL-2 exerts its biological activities through the binding to a specific receptor on target cells (42).…”

mentioning

confidence: 99%

Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling.

Kawahara¹,

Minami²,

Taniguchi³

1994

Mol. Cell. Biol.

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The high-affinity interleukin 2 receptor (IL-2R) consists of at least three distinct subunits: the IL-2R a chain (IL-2Rca), , chain (IL-2RO), and -y chain (IL-2Ry). It has been shown that the cytoplasmic region of IL-2RP, but not of IL-2Ra, is essential for IL-2 signalling to the cell interior. In the present study, we examined the functional role of the IL-2R-y cytoplasmic region in the IL-3-dependent mouse hematopoietic cell line BAF-B03, which expresses the endogenous IL-2Ra and IL-2R-y, or its subline F7, which additionally expresses human IL-2RP cDNA. We show that overexpression of a mutant IL-2R-y, lacking all but 7 amino acids of its cytoplasmic region, results in the selective inhibition of IL-2-induced c-fos gene activation and cellular proliferation in F7 cells. When two chimeric receptor molecules in which the cytoplasmic regions of IL-2RP and IL2R,y had been swapped with each other (IL-2RI/y and IL-2Ry/0) were coexpressed in BAF-B03, the cells responded to IL-2. These results indicate the critical importance of the IL-2-induced functional cooperation of the two cytoplasmic regions. Finally, we provide evidence that the IL-2R-y cytoplasmic region is also critical for the IL-4-and IL-7-induced growth signal transduction in BAF-B03.

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mentioning

confidence: 99%

Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling.

Kawahara¹,

Minami²,

Taniguchi³

1994

Mol. Cell. Biol.

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“…Interleukin 2 (IL-2) exerts its effects through binding to the functional IL-2 receptor (IL-2R) (1,2). At least three IL-2R components have been identified: the a chain (IL-2Ra) (3)(4)(5), the p chain (IL-2Rp) (6), and the ychain (IL-2Ry) (7).…”

mentioning

confidence: 99%

Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction.

Kobayashi

Kono

Hatakeyama

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

123

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The binding of interleukin 2 (IL-2) to the IL-2 receptor (IL-2R) induces a rapid increase in tyrosine phosphorylation of cellular proteins. In a previous study, we have shown that p56Ick (lck), a src-family protein tyrosine kinase (src-PTK), physically and functionally associates with the IL-2R (3 chain (IL-2Rf3). To further investigate a role of src-PTKs in IL-2 signaling, we analyzed a mouse pro-B-cell line, in which Ick is not expressed detectably. We observed that in this cell line, IL-2 induces activation of at least two src-PTKs, p59fYn (fyn) and p53/56iYn (lyn). Interestingly, stimulation of this cell line with IL-3 also induces activation of src-PTKs. The activation offtn or lyn seems to be selective for stimulation with IL-2 or IL-3 since stimulation with IL-6 fails to activate them. Furthermore, we provide evidence for the physical association offyn with IL-2R13. Taken together with previous results, our current study suggests that different src-PTKs, each of which is expressed in a cell-type-specific manner, can participate in the IL-2 signal transduction.

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“…IL-2 promotes the proliferation of IL-2-dependent T cells and functions as an immunomodulator of activated B cells, macrophages, and natural killer cells (2). IL-2 expresses its physiological functions through interaction with its receptor complex, which consists of three receptor subunits, ␣, ␤, and ␥ (IL-2R␣, -␤, and -␥) (3).…”

Section: Interleukin-2 (Il-2)mentioning

confidence: 99%

Interleukin-2 Carbohydrate Recognition Modulates CTLL-2 Cell Proliferation

Fukushima

Yamashita

2001

Journal of Biological Chemistry

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Interleukin-2 (IL-2) specifically recognizes high-mannose type glycans with five or six mannosyl residues. To determine whether the carbohydrate recognition activity of IL-2 contributes to its physiological activity, the inhibitory effects of high-mannose type glycans on IL-2-dependent CTLL-2 cell proliferation were investigated. Man 5 GlcNAc 2 Asn added to CTLL-2 cell cultures inhibited not only phosphorylation of tyrosine kinases but also IL-2-dependent cell proliferation. We found that a complex of IL-2, IL-2 receptor ␣, ␤, ␥ subunits, and tyrosine kinases was formed in rhIL-2-stimulated CTLL-2 cells. Among the components of this complex, only the IL-2 receptor ␣ subunit was stained with Galanthus nivalis agglutinin which specifically recognizes high-mannose type glycans. This staining was diminished after digestion of the glycans with endo-␤-N-acetylglucosaminidase H or D, suggesting that at least a N-glycan containing Man 5 GlcNAc 2 is linked to the extracellular portion of the IL-2 receptor ␣ subunit. Our findings indicate that IL-2 binds the IL-2 receptor ␣ subunit through Man 5 GlcNAc 2 and a specific peptide sequence on the surface of CTLL-2 cells. When IL-2 binds to the IL-2R␣ subunit, this may trigger formation of the high affinity complex of IL-2-IL-2R␣, -␤, and -␥ subunits, leading to cellular signaling.

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Molecular Analysis of the Interleukin‐2 System

Cited by 85 publications

References 43 publications

Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling.

Evidence for a critical role for the cytoplasmic region of the interleukin 2 (IL-2) receptor gamma chain in IL-2, IL-4, and IL-7 signalling.

Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction.

Interleukin-2 Carbohydrate Recognition Modulates CTLL-2 Cell Proliferation

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