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.
Copyright 2001 S. Karger AG, Basel
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Binding Sites
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DNA-Binding Proteins / metabolism*
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Enzyme Induction
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Humans
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Interleukin-15 / metabolism*
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Interleukin-15 / pharmacology
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Interleukin-2 / metabolism*
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Interleukin-2 / pharmacology
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Intracellular Signaling Peptides and Proteins
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Milk Proteins*
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Mycosis Fungoides / immunology*
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Phosphoproteins / metabolism*
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / biosynthesis*
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Proteins / pharmacology
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STAT5 Transcription Factor
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Skin Neoplasms / immunology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism*
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Trans-Activators / metabolism*
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Tumor Cells, Cultured
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Tumor Suppressor Proteins
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Tyrosine / metabolism
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src-Family Kinases / antagonists & inhibitors
Substances
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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GAB2 protein, human
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Interleukin-15
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Interleukin-2
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Intracellular Signaling Peptides and Proteins
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Milk Proteins
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Phosphoproteins
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Proteins
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STAT5 Transcription Factor
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STAT5A protein, human
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Trans-Activators
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Tumor Suppressor Proteins
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phosphoprotein phosphatase inhibitor 1
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Tyrosine
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src-Family Kinases
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PTPN11 protein, human
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases