Leukemia inhibitory factor (LIF) and oncastsin M (OSM) high affinity binding require additional receptor subunits besides GP130 and GP190.
The structure of Leukaemia Inhibitory Factor (LIF) and Oncostatin M (OSM) receptors is not completely resolved. Heterodimerization of gp190 and gp130 has been proposed to form a high affinity receptor (type I) shared by LIF and OSM, while heterodimerization of gp130 with an as yet unidentified subunit is proposed to form a high affinity OSM receptor (type II) not shared by LIF. We have analysed the binding stoichiometries, cross-competition properties and cross-linking patterns of LIF and OSM to the choriocarcinoma JAR cell line. The data obtained are not fully accounted for by the model proposed above. They indicate rather that third chains of 140-150 kDa molecular mass, in addition to the gp130 and gp190 subunits, enter in the structure of LIF and OSM high affinity receptors. These results were strongly supported by transfection experiments in CHO cells. CHO cells co-transfected with the human gp190 and gp130 cDNAs expressed high affinity LIF receptors but no high-affinity OSM receptors, indicating that an additional component is required for high affinity OSM binding. High-affinity LIF cross-linking on these cells also showed the association of LIF with a 150 kDa component in addition to the gp130 and gp190 subunits.
Heymann
D
D
IMSERM, Institut de Biologie, Quai Moncousu, France.
Godard
A
A
Raher
S
S
Bentouimou
N
N
Blanchard
F
F
Cherel
M
M
Hallet
M M
MM
Jacques
Y
Y
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism*; D046911:Macromolecular Substances; D008961:Models, Structural; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D003432:Cross-Linking Reagents; D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D046911:Macromolecular Substances; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins; D053683:Oncostatin M