LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor.
The ciliary neurotrophic factor (CNTF) receptor complex is shown here to include the CNTF binding protein (CNTFR alpha) as well as the components of the leukemia inhibitory factor (LIF) receptor, LIFR beta (the LIF binding protein) and gp130 [the signal transducer of interleukin-6 (IL-6)]. Thus, the conversion of a bipartite LIF receptor into a tripartite CNTF receptor apparently occurs by the addition of the specificity-conferring element CNTFR alpha. Both CNTF and LIF trigger the association of initially separate receptor components, which in turn results in tyrosine phosphorylation of receptor subunits. Unlike the IL-6 receptor complex in which homodimerization of gp130 appears to be critical for signal initiation, signaling by the CNTF and LIF receptor complexes depends on the heterodimerization of gp130 with LIFR beta. Ligand-induced dimerization of signal-transducing receptor components, also seen with receptor tyrosine kinases, may provide a general mechanism for the transmission of a signal across the cell membrane.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
S
S
Davis
T H
TH
Aldrich
N
N
Stahl
L
L
Pan
T
T
Taga
T
T
Kishimoto
N Y
NY
Ip
G D
GD
Yancopoulos
D000818:Animals; D015703:Antigens, CD; D002460:Cell Line; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D010766:Phosphorylation; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D050822:Cytokine Receptor gp130; D014443:Tyrosine