Identification of a 130-kilodalton tyrosine-phosphorylated protein induced by interleukin-11 as JAK2 tyrosine kinase, which associates with gp130 signal transducer.
Interleukin-11 (IL-11) shares the common signal transducer gp130 with IL-6, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and triggers activation of unknown tyrosine kinases as the early steps of signal transduction pathway. Here we identify a 130-kilodalton tyrosine-phosphorylated protein induced by IL-11 in 3T3-L1 cells as JAK2 tyrosine kinase. We further show that the in vitro kinase activity of JAK2 is greatly enhanced following stimulation with IL-11 in 3T3-L1 cells and TF-1 cells. Furthermore, we demonstrate that JAK2 physically associates with the signal transducer gp130. Similar results were observed following stimulation with IL-6, LIF, and OSM. However, we were unable to show that JAK1 is tyrosine phosphorylated and activated by IL-11 under identical conditions. These results suggest that JAK2 tyrosine kinase is one of the tyrosine kinases involved in signal transduction mediated by IL-11, IL-6, LIF, and OSM.
Yin
T
T
Department of Medicine (Hematology/Oncology), Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202.
Yasukawa
K
K
Taga
T
T
Kishimoto
T
T
Yang
Y C
YC
D015703:Antigens, CD; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D053614:Janus Kinase 2; D053605:Leukemia Inhibitory Factor; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D015703:Antigens, CD; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D011518:Proto-Oncogene Proteins; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2