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The soluble interleukin‐6 receptor is generated by shedding

The soluble interleukin‐6 receptor is generated by shedding The ligand‐binding subunit (gp80) of the human interleukin‐6 receptor (IL‐6R) was transiently expressed in COS‐7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS‐7 cells after purification to homogeneity and N‐terminal sequencing as a soluble form of the gp80/IL‐6R. Shedding of the gp80 protein was strongly induced by 4β‐phorbol‐12‐myristate‐13‐acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co‐transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS‐7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS‐7 cells is a specific process. The shed gp80 protein specifically binds IL‐6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC‐regulated shedding is the physiological mechanism of generation of the soluble IL‐6R. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Immunology Wiley

The soluble interleukin‐6 receptor is generated by shedding

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References (64)

Publisher
Wiley
Copyright
Copyright © 1993 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
0014-2980
eISSN
1521-4141
DOI
10.1002/eji.1830230226
pmid
8436181
Publisher site
See Article on Publisher Site

Abstract

The ligand‐binding subunit (gp80) of the human interleukin‐6 receptor (IL‐6R) was transiently expressed in COS‐7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS‐7 cells after purification to homogeneity and N‐terminal sequencing as a soluble form of the gp80/IL‐6R. Shedding of the gp80 protein was strongly induced by 4β‐phorbol‐12‐myristate‐13‐acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co‐transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS‐7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS‐7 cells is a specific process. The shed gp80 protein specifically binds IL‐6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC‐regulated shedding is the physiological mechanism of generation of the soluble IL‐6R.

Journal

European Journal of Immunology – Wiley

Published: Feb 1, 1993

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