Biosynthetic and glycosylation events of the IL-6 receptor beta-subunit, gp130.
It is now recognized that the beta-subunit of the interleukin-6 (IL-6) receptor, also known as gp130, is a common signal transducer shared by other cytokines, including ciliary neurotrophic factor, leukemia inhibitor factor, oncostatin M, and IL-11. In this study, the biosynthesis and glycosylation of hepatic gp130 were investigated using a specific polyclonal antibody to the 287 amino acid cytoplasmic domain of gp130. Immunoprecipitation and metabolic labeling experiments demonstrate, in addition to a mature surface expressed gp130, the presence of a major immature form of the molecule within the cell. The immature form can shift to become a functional gp130 only after being terminally glycosylated. The kinetics of gp130 maturation and surface expression were determined. When both forms of gp130 are deglycosylated the resulting core peptides migrate to identical positions in a denatured protein gel, indicating that the principal difference between the two forms resides in the extent of their glycosylation. IL-6 and other members of this cytokine family activate only the mature form, demonstrating its location at the membrane surface. Protein and mRNA turnover studies reveal gp130 to be a stable, slowly renewing population under nonstimulated conditions. These findings provide novel information on the intracellular events leading to the expression of this critically important signal transducing protein.
Wang
Y
Y
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.
Fuller
G M
GM
D000581:Amidohydrolases / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015703:Antigens, CD; D001345:Autoradiography; D015153:Blotting, Western; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D006031:Glycosylation / Q000187:drug effects; D006207:Half-Life; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D019947:Receptors, Interleukin-6; D015398:Signal Transduction / Q000502:physiology*; D014415:Tunicamycin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D014415:Tunicamycin; D050822:Cytokine Receptor gp130; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase