Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor.
Specific low-affinity receptors for leukemia inhibitory factor (LIF), oncostatin M (OSM; gp130), and ciliary neurotrophic factor (CNTF; receptor alpha, CNTFR alpha) may be utilized in various combinations to generate high-affinity binding sites and signal transduction. We have tested the ability of combinations of these receptors to transduce a proliferative signal in BAF-B03 cells. Coexpression of the LIF receptor and gp130 in these cells conferred high-affinity LIF and OSM binding and responsiveness to LIF and OSM. These cells also responded to CNTF in the absence of detectable binding. The further addition of CNTFR alpha conferred high-affinity CNTF binding and enhanced responsiveness to CNTF but did not modify responses to LIF or OSM. Coexpression of LIF receptor and CNTFR alpha resulted in a nonfunctional high-affinity binding site. These data are consistent with a role for the CNTFR alpha in enhancing CNTF action but the CNTFR alpha is not absolutely required for CNTF action and suggest a wider range of targets for CNTF.
Gearing
D P
DP
Immunex Research and Development Corporation, Seattle, WA 98101.
Ziegler
S F
SF
Comeau
M R
MR
Friend
D
D
Thoma
B
B
Cosman
D
D
Park
L
L
Mosley
B
B
D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D006131:Growth Inhibitors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D051379:Mice; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D015398:Signal Transduction; D014162:Transfection
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; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D017978:Receptors, Growth Factor; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M