Signal transduction through homo- or heterodimers of gp130.
One of the characteristic features of cytokines is their functional pleiotropy and redundancy which can now be explained on the molecular basis of the cytokine receptor system. The cytokine receptor system usually consists of two polypeptide chains, a ligand specific receptor and a common signal transducer. The IL-6 receptor system consists of an 80 kDa IL-6 receptor and a gp130 which functions as a signal transducer not only for IL-6R but also for LIF, OSM, ciliary neurotrophic factor (CNTF), and IL-11 receptors. Interaction of IL-6 and IL-6 receptor induces homodimerization of gp130 which interacts and activates an intracytoplasmic tyrosine kinase, JAK-1 kinase. A downstream substrate of JAK kinase in hepatocytes is acute phases responsive factor (APRF)/STAT3. After tyrosine specific phosphorylation of APRF, it translocates into nuclei, binds to type 2 IL-6 responsive element and induces acute phase gene expression. In order to study in vivo roles of the signaling molecules, targeted disruptions of the genes encoding gp130 and NF IL-6 were carried out. The result revealed the essential role of gp130 in hemopoiesis and heart muscle development. NF IL-6 was shown to be essential for bactericidal function of macrophages.
Kishimoto
T
T
Osaka University Medical School, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D003001:Cloning, Molecular; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000235:genetics; D018390:Gene Targeting; D053613:Janus Kinase 1; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1