Interleukin-6 and ciliary neurotrophic factor trigger janus kinase activation and early gene response in rat hepatocytes.
Interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) share a signal-transducing molecule called gp130. Previous studies showed that CNTF regulates fibrinogen gene expression in rat hepatocytes by competitive binding to the IL-6 receptor. This report explores the post ligand-binding events in the control of fibrinogen and early response gene production stimulated by IL-6 and CNTF in primary rat hepatocytes. Metabolic labeling, using [32P]orthophosphate or anti-phosphotyrosine antibody (Ab) blot experiments revealed that both IL-6 and CNTF induced tyrosine phosphorylation of gp130, and the Jak1 and Jak2 kinases in a dose- and time-dependent manner. Additional experiments revealed that only one of the early response genes, junb, but not c-myc or c-fos, was stimulated by the addition of either IL-6 or CNTF. These data suggest that activation of Jak kinases and stimulation of junb reflect a divergence of the IL-6/CNTF signaling pathway and further suggest that junb may participate in cytokine control of acute-phase protein production in the inflammatory response.
Wang
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Y
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.
Fuller
G M
GM
D000210:Acute-Phase Reaction; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017781:Genes, Immediate-Early; D016758:Genes, jun; D019833:Genistein; D015850:Interleukin-6 / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D004791:Enzyme Inhibitors; C494201:Il6st protein, rat; D015850:Interleukin-6; D007529:Isoflavones; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D050822:Cytokine Receptor gp130; D019000:Phosphotyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C507906:Jak1 protein, rat; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2