Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-3-22
pubmed:abstractText
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 4 beta-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
473-80
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8436181-Cell Line, pubmed-meshheading:8436181-Cells, Cultured, pubmed-meshheading:8436181-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:8436181-Fluorescent Antibody Technique, pubmed-meshheading:8436181-Gene Expression, pubmed-meshheading:8436181-Humans, pubmed-meshheading:8436181-Interleukin-6, pubmed-meshheading:8436181-Membrane Glycoproteins, pubmed-meshheading:8436181-Monocytes, pubmed-meshheading:8436181-Plasmids, pubmed-meshheading:8436181-Protease Inhibitors, pubmed-meshheading:8436181-Protein Kinase C, pubmed-meshheading:8436181-Receptors, Immunologic, pubmed-meshheading:8436181-Receptors, Interleukin-6, pubmed-meshheading:8436181-Solubility, pubmed-meshheading:8436181-Tetradecanoylphorbol Acetate, pubmed-meshheading:8436181-Transfection, pubmed-meshheading:8436181-Viral Envelope Proteins
pubmed:year
1993
pubmed:articleTitle
The soluble interleukin-6 receptor is generated by shedding.
pubmed:affiliation
Institut für Biochemie, RWTH Aachen, FRG.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't