SHP2 regulates IL-2 induced MAPK activation, but not Stat3 or Stat5 tyrosine phosphorylation, in cutaneous T cell lymphoma cells

Johannes Lundin Brockdorff, Anders Woetmann, Tomas Mustelin, Keld Kaltoft, Qian Zhang, Mariusz A Wasik, Carsten Röpke, Niels Ødum

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13 Citations (Scopus)

Abstract

The phosphotyrosine phosphatase SHP2 has been suggested to regulate activation of MAPK, Stat3, and Stat5 in several experimental models. In this study we investigated the role of SHP2 in IL-2 induced activation of MAPK and the Stat proteins using the human CTCL cell line MyLa2059 derived from a cutaneous T cell lymphoma (CTCL). For this purpose, MyLa2059 cells were stably transfected with wild-type SHP2 or inactive SHP2. The cells transfected with inactive SHP2 showed reduced MAPK activation upon IL-2 stimulation, suggesting that SHP2 upregulates IL-2 induced MAPK activation in T cells. However, the constitutive tyrosine phosphorylation of Stat3 as well as IL-2 induced Stat5 tyrosine phosphorylation and DNA binding were unaffected by the stably transfected wild-type SHP2 as well as the inactive SHP2. In conclusion, we show for the first time that SHP2 positively regulates IL-2 induced MAPK activation in malignant T cells. Furthermore, the results indicate that SHP2 may not be involved in the activation of Stat3 or Stat5 in CTCL cells.
Original languageEnglish
JournalCytokine
Volume20
Issue number4
Pages (from-to)141-7
Number of pages6
ISSN1043-4666
DOIs
Publication statusPublished - 2002

Bibliographical note

Keywords: Amino Acid Substitution; DNA, Neoplasm; DNA-Binding Proteins; Enzyme Activation; Humans; Interleukin-2; Intracellular Signaling Peptides and Proteins; MAP Kinase Kinase Kinase 1; MAP Kinase Signaling System; Milk Proteins; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Mutation, Missense; Mycosis Fungoides; Neoplasm Proteins; Phosphorylation; Protein Binding; Protein Processing, Post-Translational; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases; Protein-Serine-Threonine Kinases; Recombinant Fusion Proteins; STAT3 Transcription Factor; STAT5 Transcription Factor; Trans-Activators; Transfection; Tumor Cells, Cultured

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