Cloning and characterization of a specific receptor for mouse oncostatin M.
Oncostatin M (OSM) is a member of a family of cytokines that includes ciliary neurotrophic factor, interleukin-6, interleukin-11, cardiotrophin-1, and leukemia inhibitory factor (LIF). The receptors for these cytokines consist of a common signaling subunit, gp130, to which other subunits are added to modify ligand specificity. We report here the isolation and characterization of a cDNA encoding a subunit of the mouse OSM receptor. In NIH 3T3 cells (which endogenously express gp130, LIF receptor beta [LIFRbeta], and the protein product, c12, of the cDNA described here), mouse LIF, human LIF, and human OSM signaled through receptors containing the LIFRbeta and gp130 but not through the mouse OSM receptor. Mouse OSM, however, signaled only through a c12-gp130 complex; it did not use the LIF receptor. Binding studies demonstrated that mouse OSM associated directly with either the c12 protein or gp130. These data highlight the species-specific differences in receptor utilization and signal transduction between mouse and human OSM. In mouse cells, only mouse OSM is capable of activating the mouse OSM receptor; human OSM instead activates the LIF receptor. Therefore, these data suggest that all previous studies with human OSM in mouse systems did not elucidate the biology of OSM but, rather, reflected the biological actions of LIF.
Lindberg
R A
RA
Department of Immunology, Amgen, Inc., Thousand Oaks, California 91320-1789, USA.
Juan
T S
TS
Welcher
A A
AA
Sun
Y
Y
Cupples
R
R
Guthrie
B
B
Fletcher
F A
FA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D016415:Sequence Alignment; D015398:Signal Transduction; D013045:Species Specificity; D054804:Cathelicidins
D015703:Antigens, CD; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008562:Membrane Glycoproteins; D053683:Oncostatin M; D010455:Peptides; D011498:Protein Precursors; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; C084994:NPG4 protein, Sus scrofa; D054804:Cathelicidins; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; C507837:LIF protein, human; C507840:LIFR protein, human; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; C508351:OSM protein, human; C508352:Osm protein, mouse