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  • 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.
    Author: Brockdorff JL, Gu H, Mustelin T, Kaltoft K, Geisler C, Röpke C, Ødum N.
    Journal: Exp Clin Immunogenet; 2001; 18(2):86-95. PubMed ID: 11340297.
    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 beta-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.
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