Linked Life Data

12393492

Source:http://linkedlifedata.com/resource/pubmed/id/12393492

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-1-31
pubmed:abstractText
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the production and functional activity of granulocytes and macrophages, properties that have encouraged its clinical use in bone marrow transplantation and in certain infectious diseases. Despite the importance of GM-CSF in regulating myeloid cell numbers and function, little is known about the exact composition and mechanism of assembly of the GM-CSF receptor complex. We have now produced soluble forms of the GM-CSF receptor alpha chain (sGMRalpha) and beta chain (sbetac) and utilized GM-CSF, the GM-CSF antagonist E21R (Glu21Arg), and the betac-blocking monoclonal antibody BION-1 to define the molecular assembly of the GM-CSF receptor complex. We found that GM-CSF and E21R were able to form low-affinity, binary complexes with sGMRalpha, each having a stoichiometry of 1:1. Importantly, GM-CSF but not E21R formed a ternary complex with sGMRalpha and sbetac, and this complex could be disrupted by E21R. Significantly, size-exclusion chromatography, analytical ultracentrifugation, and radioactive tracer experiments indicated that the ternary complex is composed of one sbetac dimer with a single molecule each of sGMRalpha and of GM-CSF. In addition, a hitherto unrecognized direct interaction between betac and GM-CSF was detected that was absent with E21R and was abolished by BION-1. These results demonstrate a novel mechanism of cytokine receptor assembly likely to apply also to interleukin-3 (IL-3) and IL-5 and have implications for our molecular understanding and potential manipulation of GM-CSF activation of its receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1308-15
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12393492-Animals, pubmed-meshheading:12393492-Baculoviridae, pubmed-meshheading:12393492-Binding Sites, pubmed-meshheading:12393492-Chromatography, Gel, pubmed-meshheading:12393492-Cloning, Molecular, pubmed-meshheading:12393492-DNA, Complementary, pubmed-meshheading:12393492-Dimerization, pubmed-meshheading:12393492-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12393492-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:12393492-Humans, pubmed-meshheading:12393492-Isotope Labeling, pubmed-meshheading:12393492-Molecular Structure, pubmed-meshheading:12393492-Phosphorus Radioisotopes, pubmed-meshheading:12393492-Polymerase Chain Reaction, pubmed-meshheading:12393492-Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:12393492-Recombinant Proteins, pubmed-meshheading:12393492-Solubility, pubmed-meshheading:12393492-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:12393492-Spodoptera, pubmed-meshheading:12393492-Transfection, pubmed-meshheading:12393492-Ultracentrifugation
pubmed:year
2003
pubmed:articleTitle
Molecular assembly of the ternary granulocyte-macrophage colony-stimulating factor receptor complex.
pubmed:affiliation
Cytokine Receptor Laboratory and Protein Laboratory, Division of Human Immunology, Institute of Medical and Veterinary Science (IMVS), Adelaide, South Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't