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• W1899485875 endingPage "4318" @default.
• W1899485875 startingPage "4312" @default.
• W1899485875 abstract "Abstract From the sequence of human IL-2 we have recently characterized a peptide (p1–30), which is the first IL-2 mimetic described. P1–30 covers the entire α helix A of IL-2 and spontaneously folds into a α helical homotetramer mimicking the quaternary structure of a hemopoietin. This neocytokine interacts with a previously undescribed dimeric form of the human IL-2 receptor β-chain likely to form the p1–30 receptor (p1–30R). P1–30 acts as a specific IL-2Rβ agonist, selectively inducing activation of CD8 and NK lymphocytes. From human PBMC we have also shown that p1–30 induces the activation of lymphokine-activated killer cells and the production of IFN-γ. Here we demonstrate the ability of p1–30 to act in synergy with IL-2, -4, -9, and -15. These synergistic effects were analyzed at the functional level by using TS1β, a murine T cell line endogenously expressing the common cytokine γ gene and transfected with the human IL-2Rβ gene. At the receptor level, we show that expression of human IL-2Rβ is absolutely required to obtain synergistic effects, whereas IL-2Rα specifically impedes the synergistic effects obtained with IL-2. The results suggest that overexpression of IL-2Rα inhibits p1–30R formation in the presence of IL-2. Finally, concerning the molecular effects, although p1–30 alone induces the antiapoptotic molecule bcl-2, we show that it does not influence mRNA expression of c-myc, c-jun, and c-fos oncogenes. In contrast, p1–30 enhances IL-2-driven expression of these oncogenes. Our data suggest that p1–30R (IL-2Rβ)2 and intermediate affinity IL-2R (IL-2Rβγ), when simultaneously expressed at the cell surface, may induce complementary signal transduction pathways and act in synergy." @default.
• W1899485875 created "2016-06-24" @default.
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• W1899485875 date "2000-10-15" @default.
• W1899485875 modified "2023-10-12" @default.
• W1899485875 title "IL-2Rβ Agonist P1–30 Acts in Synergy with IL-2, IL-4, IL-9, and IL-15: Biological and Molecular Effects" @default.
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• W1899485875 doi "https://doi.org/10.4049/jimmunol.165.8.4312" @default.
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• W1899485875 hasPublicationYear "2000" @default.
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