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

Exp Clin Immunogenet. 2001;18(2):86-95. doi: 10.1159/000049187.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Binding Sites
  • DNA-Binding Proteins / metabolism*
  • Enzyme Induction
  • Humans
  • Interleukin-15 / metabolism*
  • Interleukin-15 / pharmacology
  • Interleukin-2 / metabolism*
  • Interleukin-2 / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Milk Proteins*
  • Mycosis Fungoides / immunology*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / biosynthesis*
  • Proteins / pharmacology
  • STAT5 Transcription Factor
  • Skin Neoplasms / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins
  • Tyrosine / metabolism
  • src-Family Kinases / antagonists & inhibitors

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • GAB2 protein, human
  • Interleukin-15
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Milk Proteins
  • Phosphoproteins
  • Proteins
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Trans-Activators
  • Tumor Suppressor Proteins
  • phosphoprotein phosphatase inhibitor 1
  • Tyrosine
  • src-Family Kinases
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases