SHP2 regulates IL-2 induced MAPK activation, but not Stat3 or Stat5 tyrosine phosphorylation, in cutaneous T cell lymphoma cells.
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.
Lundin Brockdorff
Johannes
J
Institute of Medical Microbiology and Immunology, University of Copenhagen, Blegdamsvej 3c, 2200 Copenhagen-N, Denmark.
Woetmann
Anders
A
Mustelin
Tomas
T
Kaltoft
Keld
K
Zhang
Qian
Q
Wasik
Mariusz A
MA
Röpke
Carsten
C
Ødum
Niels
N
D019943:Amino Acid Substitution; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D048728:MAP Kinase Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020125:Mutation, Missense; D009182:Mycosis Fungoides / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases