Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation.
Oncostatin M (OSM) is a cytokine whose structural and functional features are similar to other members of the interleukin (IL)-6 family of cytokines (IL-6, IL-11, leukemia inhibitory factor (LIF), granulocyte colonystimulating factor, ciliary neurotrophic factor, and cardiotrophin-1), many of which utilize gp130 as a common receptor subunit. A biologically active OSM receptor has been previously described that consists of a heterodimer of leukemia inhibitory factor receptor (LIFR) and gp130. This LIFR.gp130 complex is also a functional receptor for LIF. We have cloned and characterized an alternative subunit (OSMRbeta) for an OSM receptor complex (a heterodimer of gp130 and OSMRbeta) that is activated by OSM but not by LIF. The signaling capability of specific receptor subunit combinations was analyzed by independent assays measuring cell proliferation or induction of acute phase protein synthesis. Our results demonstrate that both LIF and OSM cause tyrosine phosphorylation and activation of the gp130.LIFR combination, but the gp130.OSMRbeta complex is activated by OSM only. OSM-induced cellular responses, initiated through low affinity binding to gp130, are mediated by two heterodimeric receptor complexes that utilize alternative signal transducing subunits that confer different cytokine specificities to the receptor complex.
Mosley
B
B
Immunex Corporation, Seattle, Washington 98101, USA.
De Imus
C
C
Friend
D
D
Boiani
N
N
Thoma
B
B
Park
L S
LS
Cosman
D
D
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D003001:Cloning, Molecular; D015870:Gene Expression; D006131:Growth Inhibitors; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; 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; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M