Tyrosine phosphorylation and activation of JAK family tyrosine kinases by interleukin-9 in MO7E cells.
Interleukin-9 (IL-9) is a T-cell-derived multifunctional cytokine that can stimulate the proliferation of a human megakaryocytic leukemia cell line, MO7E. Previous studies suggested that protein tyrosine phosphorylation may be involved in IL-9 signaling pathways. However, tyrosine kinases activated by IL-9 have not been identified. In this report we show that IL-9 induces tyrosine phosphorylation and activation of the JAK family tyrosine kinases including JAK1, JAK3, and Tyk2. The kinetic studies indicate that tyrosine phosphorylation and activation of JAK kinases induced by IL-9 occurred within 1 minute, peaked by 5 to 10 minutes, and persisted at least for 45 minutes. Furthermore, we show that signal transducers and activators of transcription (Stat) 91 or related protein and an 88-kD Stat 91-associated protein are rapidly tyrosine phosphorylated following IL-9 treatment. Gel shift assays confirm that nuclear extracts from MO7E cells stimulated with IL-9 specifically interact with a DNA element termed gamma activated site. These results suggest that actions of IL-9 may, in part, be mediated through JAK kinase-Stat signaling cascades.
Yin
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Walther Oncology Center, Indiana University Medical Center, Indianapolis 46202, USA.
Yang
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Yang
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YC
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D016906:Interleukin-9 / Q000494:pharmacology*; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D007947:Leukemia, Megakaryoblastic, Acute / Q000201:enzymology* / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004268:DNA-Binding Proteins; D016906:Interleukin-9; D009363:Neoplasm Proteins; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human