Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells.
Interleukin-6 (IL-6) induces the expression of acute phase plasma protein genes in hepatic cells through the action of gp130, the signal-transducing subunit of the IL-6 receptor. To identify whether the transmembrane domain of gp130 is required for signaling function, cytoplasmic forms of gp130 were constructed that consisted of the tetramerizing N-terminal domain of Bcr linked to the transmembrane and cytoplasmic domains of gp130 (Bcr/gp130) or just to the cytoplasmic domain of gp130 (Bcr/gp130DeltaTM). The expression and function of both constructs were determined in transiently transfected COS-1 and HepG2 cells. Bcr/gp130 is capable of interacting with JAK1, JAK2, and TYK2; is constitutively active; and induces gene expression through IL-6-responsive elements. In contrast, Bcr/gp130DeltaTM, while expressed at a higher level than Bcr/gp130 and still able to interact with JAK1, is ineffective in recruiting the endogenous signal transduction pathways for inducing gene expression. However, Bcr/gp130DeltaTM initiates partial signaling in the presence of overexpressed JAK1 and TYK2, but not JAK2. The data suggest that the transmembrane domain of gp130 is necessary for signal transduction and determines the interaction with members of the Janus kinase family.
Kim
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Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Baumann
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D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry; D050822:Cytokine Receptor gp130; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008099:Liver / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D051562:Proto-Oncogene Proteins c-bcr