Protein kinase C activity is rate limiting for shedding of the interleukin-6 receptor

• Published in: Biochemical and biophysical research communications Vol. 189; no. 2; pp. 794 - 800
• Main Authors: Müllberg, Jürgen, Schooltink, Heidi, Stoyan, Tanja, Heinrich, Peter C., Rose-John, Stefan
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.12.1992; Elsevier
• Subjects: Alkaloids - pharmacology; Animals; Binding Sites; Biological and medical sciences; Carcinoma, Hepatocellular; Cell Line; Cell receptors; Cell structures and functions; Cycloheximide - pharmacology; cytokines; Fundamental and applied biological sciences. Psychology; Humans; interleukin 6; Interleukin-6 - metabolism; Kinetics; Liver Neoplasms; Macromolecular Substances; mediation; Miscellaneous; Molecular and cellular biology; Phorbol Esters - pharmacology; protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - genetics; Protein Kinase C - metabolism; receptors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Interleukin-6; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Staurosporine; Transfection; Tumor Cells, Cultured; Interleukin 6; Ligand binding; Protein kinase C; Membrane receptor; Enzyme; Proteolysis; Protein synthesis; Cytokine; Soluble form; Release
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(92)92272-Y

An analysis of the mechanism of generation of the soluble interleukin-6 receptor (IL-6R) has been performed. The membrane-bound receptor is proteolytically cleaved to release a soluble receptor form which retained its ligand binding capacity. Furthermore, the soluble IL-6R is unique in its ability to induce a biological signal in complex with the ligand interleukin-6 (IL-6) on cells which by themselves do not bind IL-6. Shedding of the IL-6R is strongly activated by PMA and can be inhibited by the protein kinase inhibitor staurosporine. The generation of the IL-6R is not dependent on protein synthesis. The inactive PMA analogue 4-α-phorbol-12,13-didecanoate fails to induce shedding of the IL-6R. Transfection of a protein kinase C expression plasmid into IL-6R expressing cells leads to enhanced shedding of the receptor. These experiments clearly show that protein kinase C regulates shedding of the IL-6R.