Linked Life Data

11412113

Source:http://linkedlifedata.com/resource/pubmed/id/11412113

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2001-6-19
pubmed:abstractText
Gp130 is a shared signal-transducing receptor for a family of four-helix cytokines, of which interleukin-6 is a prototypic member. IL-6-type cytokines activate gp130 to elicit downstream intracellular JAK/STAT signaling cascades through formation of hetero-oligomeric receptor complexes. Interleukin-6 must first complex with its specific alpha-receptor (Ralpha) in order to bind and activate gp130. We have dissected the extracellular activation pathway of human gp130 by human IL-6 through reconstitution of soluble complexes representing intermediate and final states in the hierarchical assembly of the IL-6/IL-6Ralpha/gp130 signaling complex. To isolate these hetero-complexes, we have applied a protein engineering strategy of covalently linking IL-6 to its Ralpha, which results in a "hyperactive" single-chain complex (hyper-IL-6) which we express in both Escherichia coli and insect cells. We have determined that IL-6/IL-Ralpha and the cytokine-binding homology region (CHR) of gp130 (D2D3) form a stable trimolecular "recognition" complex (trimer) consisting of 1IL-6,1 IL-6Ralpha, and 1 gp130-CHR. Addition of the N-terminal (D1) Ig-like domain (IGD) of gp130 to the CHR results in a transition to a hexameric "activation" complex containing 2 IL-6, 2IL-6Ralpha, and 2 gp130. These results clearly demonstrate that the recognition and activation complexes are disparate hetero-oligomeric molecular species linked by the recruitment of the gp130 IGD by the unique site III epitope present on all gp130-class cytokines. The results of these studies are relevant to other members of the IL-6 family of gp130-cytokines and address a longstanding question concerning the respective roles of the gp130 CHR and IGD in assembly of the active signaling oligomer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7593-603
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11412113-Antigens, CD, pubmed-meshheading:11412113-Cytokine Receptor gp130, pubmed-meshheading:11412113-Cytokines, pubmed-meshheading:11412113-Genetic Vectors, pubmed-meshheading:11412113-Humans, pubmed-meshheading:11412113-Immunoglobulins, pubmed-meshheading:11412113-Interleukin-6, pubmed-meshheading:11412113-Kinetics, pubmed-meshheading:11412113-Macromolecular Substances, pubmed-meshheading:11412113-Membrane Glycoproteins, pubmed-meshheading:11412113-Protein Binding, pubmed-meshheading:11412113-Protein Structure, Tertiary, pubmed-meshheading:11412113-Receptors, Interleukin-6, pubmed-meshheading:11412113-Recombinant Proteins, pubmed-meshheading:11412113-Sequence Homology, Amino Acid, pubmed-meshheading:11412113-Signal Transduction, pubmed-meshheading:11412113-Surface Plasmon Resonance, pubmed-meshheading:11412113-Ultracentrifugation
pubmed:year
2001
pubmed:articleTitle
In vitro reconstitution of recognition and activation complexes between interleukin-6 and gp130.
pubmed:affiliation
Departments of Microbiology & Immunology, and Structural Biology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, California 94305-5124, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't