Protein-tyrosine phosphatase PTPepsilon C inhibits Jak-STAT signaling and differentiation induced by interleukin-6 and leukemia inhibitory factor in M1 leukemia cells.
We engineered and expressed both a wild-type and mutant cytosolic isoform of PTPepsilon (PTPepsilonC) in murine M1 leukemic cells, which can be induced to growth arrest and monocytic differentiation by interleukin (IL)-6 and leukemia inhibitory factor (LIF). Forced expression of PTPepsilonC inhibited IL-6- and LIF-induced monocytic differentiation and apoptosis in M1 cells, whereas expression of PTPepsilonM, a transmembrane isoform of PTPepsilon, did not. PTPepsilonC expression resulted in lower levels of IL-6-induced tyrosine phosphorylation of Jak1, Tyk2, gp130, and Stat3 compared with parent cells. In M1 transfectants expressing an inactive mutant of PTPepsilonC, both tyrosine phosphorylation and apoptosis induced by IL-6 and LIF were potentiated rather than inhibited. These results suggest an important role for PTPepsilonC in negative regulation of IL-6- and LIF-induced Jak-STAT signaling.
Tanuma
N
N
Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Nakamura
K
K
Shima
H
H
Kikuchi
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D053613:Janus Kinase 1; D053605:Leukemia Inhibitory Factor; D015470:Leukemia, Myeloid, Acute; D008222:Lymphokines / Q000494:pharmacology*; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D052118:Lysosomal-Associated Membrane Protein 1
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D007527:Isoenzymes; D053613:Janus Kinase 1; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D053634:TYK2 Kinase; D015534:Trans-Activators; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C507837:LIF protein, human; C052255:Lamp1 protein, mouse; C507838:Lif protein, mouse; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; C070139:TYK2 protein, human; C499356:Tyk2 protein, mouse; C490825:PTPRE protein, human; C098067:Ptpre protein, mouse