Cross-linking identifies leukemia inhibitory factor-binding protein as a ciliary neurotrophic factor receptor component.
Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are cytokines that give rise to an identical set of tyrosine-phosphorylated proteins upon addition to responsive cells. One of these proteins is the interleukin-6 signal-transducing molecule gp130, which is required for signal transduction by both CNTF and LIF. Here we identify another prominent tyrosine-phosphorylated protein as LIF receptor (LIFR) beta, which was originally cloned as a LIF-binding protein. Cross-linking experiments with iodinated factors were carried out on a cell line responsive to CNTF and LIF, as well as on COS cells that were cotransfected with various combinations of gp130, LIFR beta, and CNTF receptor (CNTFR) alpha, the previously cloned CNTF-binding protein. These experiments reveal that LIF cross-links to LIFR beta alone, as well as to gp130 when it is coexpressed with LIFR beta. However, cross-linking of CNTF to LIFR beta and gp130 is only observed in the presence of CNTFR alpha. These and other data show that the two known LIF receptor components are recruited by CNTF and CNTFR alpha to form a trimeric CNTF receptor complex.
Institute for Molecular and Cellular Biology, Osaka University, Japan.
N
N
Stahl
S
S
Davis
V
V
Wong
T
T
Taga
T
T
Kishimoto
N Y
NY
Ip
G D
GD
Yancopoulos
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor; D003432:Cross-Linking Reagents; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016366:Open Reading Frames; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection
D020934:Ciliary Neurotrophic Factor; D003432:Cross-Linking Reagents; D006131:Growth Inhibitors; D007106:Immune Sera; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D010455:Peptides; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins