Reconstitution of high affinity leukaemia inhibitory factor (LIF) receptors in haemopoietic cells transfected with the cloned human LIF receptor.
cDNA clones encoding the human leukaemia inhibitory factor (hLIF) receptor were isolated by screening a placental cDNA expression library in COS-7 cells with 125I-hLIF. The cloned LIF receptor is a member of the haemopoietin receptor family and comprises a signal sequence (44 amino acids), an extracellular region of two haemopoietin receptor domains and three fibronectin type III domains (789 amino acids), a transmembrane domain (26 amino acids) and a cytoplasmic domain (238 amino acids). The LIF receptor is expressed in COS-7 cells as a 190 kDa glycoprotein that specifically binds human LIF with low affinity, but does not bind mouse LIF. Clones encoding a soluble form of the homologous mouse LIF receptor have been isolated, suggesting complex interactions between the various forms of LIF ligand and receptor in vivo. The LIF receptor is most related to the gp130 signal-transducing component of the IL-6 receptor, a feature that may provide a molecular basis for the intertwined biologies of LIF and IL-6 in the absence of obvious structural similarly between the ligands. Mouse B9 plasmacytoma cells transfected with the human LIF receptor display novel high affinity LIF receptors that are presumed to consist of transfected receptors in association with endogenous mouse high affinity-converting subunits. Unlike the low affinity human LIF receptor, the mixed species high affinity receptor is capable of binding mouse LIF.
Gearing
D P
DP
Immunex Research and Development Corporation, Seattle, WA 98101.
VandenBos
T
T
Beckmann
M P
MP
Thut
C J
CJ
Comeau
M R
MR
Mosley
B
B
Ziegler
S F
SF
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D006131:Growth Inhibitors; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008969:Molecular Sequence Data; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000235:genetics*; D053606:Receptors, OSM-LIF; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection / Q000235:genetics*
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; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053606:Receptors, OSM-LIF