TY - JOUR

T1 - 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

AU - Brockdorff, J L

AU - Gu, H

AU - Mustelin, T

AU - Kaltoft, K

AU - Geisler, C

AU - Röpke, C

AU - Ødum, N

N1 - Keywords: Adaptor Proteins, Signal Transducing; Binding Sites; DNA-Binding Proteins; Enzyme Induction; Humans; Interleukin-15; Interleukin-2; Intracellular Signaling Peptides and Proteins; Milk Proteins; Mycosis Fungoides; Phosphoproteins; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases; Proteins; STAT5 Transcription Factor; Skin Neoplasms; T-Lymphocytes; Trans-Activators; Tumor Cells, Cultured; Tumor Suppressor Proteins; Tyrosine; src-Family Kinases

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 11340297

VL - 18

SP - 86

EP - 95

JO - Experimental and Clinical Immunogenetics

JF - Experimental and Clinical Immunogenetics

SN - 0254-9670

IS - 2

ER -