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- W4313333735 abstract "Abstract IL-4 is a cytokine with important antiapoptotic activity. We have analyzed the role that tyrosine-containing domains within the cytoplasmic tail of IL-4Rα play in IL-4-mediated protection from apoptosis. 32D cells expressing a wt huIL-4Rα or one truncated at aa 557 were protected by huIL-4 from apoptosis while cells expressing a receptor truncated at aa 657 were not, suggesting that the carboxyl-terminal domain signals protection from apoptosis. However, changing Y713 within this region to phenylalanine had no effect. To analyze the contribution of tyrosine-containing domains independently, we transplanted regions of the huIL-4Rα to a truncated form of the huIL-2Rβ that could not signal protection from apoptosis. Transplantation of the huIL-4Rα domains containing Y497 or Y713 partially prevented cell death and together signaled protection from apoptosis in response to IL-2 as well as the wt IL-2Rβ. Mutation of Y497 and Y713 to phenylalanine inhibited protection. In contrast, transplantation of the domain containing the potential STAT6-docking tyrosines alone had no effect, yet it inhibited the protection mediated by the other domains. Although IL-4Rα signals Shc and SH2-containing inositol phosphatase (SHIP) phosphorylation, we could not establish an association between their activation and protection from apoptosis. Taken together, this study suggests that the domains of the huIL-4Rα containing Y497 and Y713 positively regulate protection from apoptosis while the domain containing the STAT6 docking sites suppresses this protection, and that additional signaling molecules other than insulin receptor substrate-1 (IRS1), Shc, or SHIP may be involved in antiapoptotic signaling." @default.
- W4313333735 created "2023-01-06" @default.
- W4313333735 creator A5000996407 @default.
- W4313333735 creator A5048079346 @default.
- W4313333735 date "1998-07-15" @default.
- W4313333735 modified "2023-10-14" @default.
- W4313333735 title "Regulation of Apoptosis by Tyrosine-Containing Domains of IL-4Rα: Y497 and Y713, But Not the STAT6-Docking Tyrosines, Signal Protection from Apoptosis" @default.
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- W4313333735 doi "https://doi.org/10.4049/jimmunol.161.2.859" @default.
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