J. Brockdorff, Haihua Gu, T. Mustelin, K. Kaltoft, C. Geisler, C. Röpke, N. Ødum
{"title":"在真菌衍生的肿瘤T细胞中,白介素-2/白介素-15刺激下Gab2在酪氨酸上磷酸化,并诱导与SHP-2和Stat5a相关","authors":"J. Brockdorff, Haihua Gu, T. Mustelin, K. Kaltoft, C. Geisler, C. Röpke, N. Ødum","doi":"10.1159/000049187","DOIUrl":null,"url":null,"abstract":"Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor β-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.","PeriodicalId":77124,"journal":{"name":"Experimental and clinical immunogenetics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000049187","citationCount":"15","resultStr":"{\"title\":\"Gab2 Is Phosphorylated on Tyrosine upon Interleukin-2/Interleukin-15 Stimulation in Mycosis-fungoides-Derived Tumor T Cells and Associates Inducibly with SHP-2 and Stat5a\",\"authors\":\"J. Brockdorff, Haihua Gu, T. Mustelin, K. Kaltoft, C. Geisler, C. Röpke, N. Ødum\",\"doi\":\"10.1159/000049187\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor β-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.\",\"PeriodicalId\":77124,\"journal\":{\"name\":\"Experimental and clinical immunogenetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2001-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1159/000049187\",\"citationCount\":\"15\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental and clinical immunogenetics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1159/000049187\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and clinical immunogenetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000049187","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Gab2 Is Phosphorylated on Tyrosine upon Interleukin-2/Interleukin-15 Stimulation in Mycosis-fungoides-Derived Tumor T Cells and Associates Inducibly with SHP-2 and Stat5a
Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor β-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.