Constitutive activation of JAK2 confers murine interleukin-3-independent survival and proliferation of BA/F3 cells.
The Janus tyrosine kinase 2 (JAK2) plays an essential role of cytokine receptor signaling, including that of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor. We reported earlier that the activation of JAK2 is essential for all the examined signals induced by human GM-CSF through the box1 region of betac, such as promotion of cell survival and proliferation. To elucidate the role of JAK2 in cell survival and proliferation, we generated an artificial activation system by constructing a chimeric molecule (beta/JAK2) consisting of betac extracellular and transmembrane regions fused with JAK2, and we analyzed various signaling events in interleukin-3-dependent mouse pro-B cell, BA/F3. The beta/JAK2 was constitutively phosphorylated in the absence of human GM-CSF and murine interleukin-3, and this led to proliferation and cell survival. Western blot analysis showed that STAT5, Shc, and SHP-2 were not phosphorylated in the cells, and the consistent activation of beta-casein and c-fos promoters was not enhanced. In contrast, c-myc transcription was constitutively activated. We propose that the activation of beta/JAK2 suffices for survival and proliferation and that the activation of STAT5 and mitogen-activated protein kinase cascade is not required for these activities in BA/F3 cells.
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Japan.
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Liu
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Itoh
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Arai
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Watanabe
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000473:pathology; D019556:COS Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D053614:Janus Kinase 2; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction / Q000187:drug effects*
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2