TY - JOUR
T1 - SHP2 regulates IL-2 induced MAPK activation, but not Stat3 or Stat5 tyrosine phosphorylation, in cutaneous T cell lymphoma cells
AU - Lundin Brockdorff, Johannes
AU - Woetmann, Anders
AU - Mustelin, Tomas
AU - Kaltoft, Keld
AU - Zhang, Qian
AU - Wasik, Mariusz A
AU - Röpke, Carsten
AU - Ødum, Niels
N1 - 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
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
U2 - 10.1006/cyto.2002.1986
DO - 10.1006/cyto.2002.1986
M3 - Journal article
C2 - 12543077
SN - 1043-4666
VL - 20
SP - 141
EP - 147
JO - Cytokine
JF - Cytokine
IS - 4
ER -