Protein tyrosine phosphorylation and activation of primary response genes by interleukin 11 in B9-TY1 cells.
Interleukin (IL) 11 is a multifunctional cytokine derived from bone marrow stromal cells. To understand the mechanisms by which IL-11 exerts its pleiotropic actions, we have analyzed IL-11-mediated signal transduction pathways in IL-11-dependent B9-TY1, which is a subclone of an IL-6-dependent B-cell hybridoma, B9. IL-11 stimulation of B9-TY1 cells resulted in tyrosine phosphorylation of a 97/95 kilodalton cellular protein in a dose-dependent manner, and this effect was inhibited by tyrosine kinase inhibitors genistein and herbimycin A, but not by a serine/threonine kinase inhibitor, H7. We next examined the early nuclear events in the IL-11-triggered intracellular signaling cascade. The data showed that tis11, tis21, and junB early response genes were rapidly activated following IL-11 treatment. The kinetic studies indicated that activation of tis11 and junB genes peaked at 30-60 min and then declined slowly afterward. The tis21 gene was constitutively expressed, and the level of tis21 mRNA was significantly increased and maintained at the elevated level following IL-11 stimulation. Inhibitor studies with genistein, herbimycin A, and H7 revealed that tyrosine kinases and H7-sensitive serine/threonine kinases are required for the IL-11-mediated activation of tis11, tis21, and junB genes. Using a variety of known protein kinase inhibitors or activators, we have demonstrated that H7-sensitive protein kinases activated by IL-11 are distinct from those of well-characterized protein kinase-second messenger systems.(ABSTRACT TRUNCATED AT 250 WORDS)
Yin
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T
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Yang
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YC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D016227:Benzoquinones; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D016758:Genes, jun; D019833:Genistein; D006825:Hybridomas / Q000378:metabolism*; D017370:Interleukin-11 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D051379:Mice; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D014158:Transcription, Genetic / Q000187:drug effects
D016227:Benzoquinones; D017370:Interleukin-11; D007529:Isoflavones; D007546:Isoquinolines; D047029:Lactams, Macrocyclic; D010879:Piperazines; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011505:Protein-Tyrosine Kinases