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.
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.
authors.affiliation: Institute for Medical Microbiology and Immunology, Harvard Medical School, Boston, Mass, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Brockdorff
authors.forename: H
authors.initials: H
authors.lastname: Gu
authors.forename: T
authors.initials: T
authors.lastname: Mustelin
authors.forename: K
authors.initials: K
authors.lastname: Kaltoft
authors.forename: C
authors.initials: C
authors.lastname: Geisler
authors.forename: C
authors.initials: C
authors.lastname: Röpke
authors.forename: N
authors.initials: N
authors.lastname: Ødum
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004790:Enzyme Induction; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism* / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D009182:Mycosis Fungoides / Q000276:immunology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D011506:Proteins / Q000494:pharmacology; D050799:STAT5 Transcription Factor; D012878:Skin Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C490895:GAB2 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D010750:Phosphoproteins; D011506:Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; C073882:phosphoprotein phosphatase inhibitor 1; D014443:Tyrosine; D019061:src-Family Kinases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases